Colorectal CarcinomaPhase 2NCT04430738
Tucatinib Plus Trastuzumab and Oxaliplatin-based Chemotherapy or Pembrolizumab-containing Combinations for HER2+ Gastrointestinal Cancers
A Phase 2 study testing tucatinib, trastuzumab and oxaliplatin in people with Colorectal Carcinoma and Gastric Adenocarcinoma, run by Seagen, a wholly owned subsidiary of Pfizer at 27 sites in 2 countries.
Trial summary
This trial studies tucatinib to find out if it is safe when given with trastuzumab and other anti-cancer drugs (pembrolizumab, FOLFOX, and CAPOX). It will look at what side effects happen when participants take this combination of drugs. A side effect is anything the drug does other than treating cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Carcinoma, Gastric Adenocarcinoma, GEJ Adenocarcinoma
- What is being tested?
- tucatinib, trastuzumab and oxaliplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 27 sitesin 2 countries
- Study dates
- 15 Sep 2020to 31 Dec 2026
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must have an unresectable or metastatic solid malignancy that is histologically or cytologically confirmed to be one of the tumor types listed below:
- Cohorts 1A, 1B, 1C, and 1D
- CRC
- Gastric adenocarcinoma
- GEJ adenocarcinoma
- Esophageal adenocarcinoma
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- Cholangiocarcinoma
- Gallbladder carcinoma
- Cohorts 1E, 1F, 1G, and 2A
- Gastric adenocarcinoma
- GEJ adenocarcinoma
- Esophageal adenocarcinoma
- Cohort 2B
- CRC
- Participants must be candidates to receive an oxaliplatin-based regimen as part of their standard-of-care treatment for all cohorts, except Cohort 1G.
- HER2+ disease, as determined by historic or local laboratory testing
- Phase 1b cohorts: measurable or non-measurable disease according to RECIST v1.1 as determined by the investigator
- Phase 2 cohorts: measurable disease according to RECIST v1.1 as determined by the investigator
- Eastern Cooperative Oncology Group Performance Status score of 0 or 1.
Who cannot join
- History of known hypersensitivity to planned study treatment
- Known to be positive for Hepatitis B or C
- For Cohorts 2A and 2B: prior anti-HER2 therapies
- For Cohorts 1E, 1F, 1G, 2A: Prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137), and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event (irAE)
- There are additional inclusion criteria. The study center will determine if criteria for participations are met.
Trial locations and contacts
27 sites in 2 countries.
27 sites in 2 countries
United States21 sites
University of New Mexico Comprehensive Cancer Center
Albuquerque, New Mexico, 87131
University of Colorado Denver CTO(CTRC)
Aurora, Colorado, 80045
University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)
Aurora, Colorado, 80045
University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)
Aurora, Colorado, 80045
University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)
Aurora, Colorado, 80045
Siteman Cancer Center - St Peters
City of Saint Peters, Missouri, 63376
Cleveland Clinic
Cleveland, Ohio, 44195
Siteman Cancer Center - West County
Creve Coeur, Missouri, 63141
PCM Trials
Denver, Colorado, 80218
Duke University Medical Center, Duke Cancer Center
Durham, North Carolina, 27710
Duke University Medical Center
Durham, North Carolina, 27710
Siteman Cancer Center - North County
Florissant, Missouri, 63031
Mayo Clinic Hospital
Phoenix, Arizona, 85054
Mayo Clinic
Scottsdale, Arizona, 85259
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
University of Washington Medical Center
Seattle, Washington, 98195
Siteman Cancer Center
St Louis, Missouri, 63108
Barnes-Jewish Hospital
St Louis, Missouri, 63110
Washington University School of Medicine
St Louis, Missouri, 63110
Siteman Cancer Center - South County
St Louis, Missouri, 63129
Sibley Memorial Hospital
Washington D.C., District of Columbia, 20016
Japan6 sites
National Cancer Center Hospital
Chuo-ku, Tokyo, 104-0045
National Cancer Center Hospital East
Kashiwa-shi, Chiba, 277-8577
St. Marianna University Hospital
Kawasaki, Kanagawa, 216-8511
Cancer Institute Hospital of Japanese Foundation for Cancer Research.
Koto-ku, Tokyo, 135-8550
Aichi Cancer Center Hospital
Nagoya, Aichi-ken, 464-8681
Osaka International Cancer Institute
Osaka, Osaka, 541-8567
About this study
Official title: A Phase 1b/2 Dose Escalation and Expansion Study of Tucatinib in Combination With Trastuzumab and Oxaliplatin-based Chemotherapy or Pembrolizumab-containing Combinations for HER2+ Gastrointestinal Cancers
This trial studies tucatinib to find out if it is safe when given with trastuzumab and other anti-cancer drugs (pembrolizumab, FOLFOX, and CAPOX). It will look at what side effects happen when participants take this combination of drugs. A side effect is anything the drug does other than treating cancer. It will also look at whether tucatinib works with these drugs to treat certain types of cancer.
The participants in this trial have HER2-positive (HER2+) cancer in their gut, stomach, intestines, or gallbladder (gastrointestinal cancer).
- Conditions
- Colorectal Carcinoma, Gastric Adenocarcinoma, GEJ Adenocarcinoma, Esophageal Adenocarcinoma, Cholangiocarcinoma, Gallbladder Carcinoma
- Being tested
- tucatinib, trastuzumab, oxaliplatin, leucovorin, fluorouracil
- Keywords
- HER2+, HER2-positive, CRC, Gastric cancer, Esophageal cancer, Seattle Genetics
- Medical subject headings
- Colorectal Neoplasms, Adenocarcinoma Of Esophagus, Cholangiocarcinoma, Gallbladder Neoplasms, Stomach Neoplasms, Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tucatinibDrug
Also called TUKYSA
For Cohort 1A, 150 mg will be administered twice daily by mouth (orally) from Cycle 1 Day 8 onwards. For all other cohorts, 300 mg (or intermediate dose) will be given orally twice daily starting on Cycle 1 Day 1.
trastuzumabDrug
Cohorts 1A and 1B: a 6 mg/kg loading dose will be given into the vein (IV; intravenously) on Cycle 1 Day 1, followed by a dose of 4 mg/kg IV every 2 weeks starting on Cycle 2 Day 1. Cohorts 1C, 1D, 1E, 1F, 1G, 2A, and 2B: an 8 mg/kg loading dose will be administered IV on Cycle 1 Day 1, followed by a dose of 6 mg/kg IV every 3 weeks thereafter.
oxaliplatinDrug
85 mg/m^2 given IV every 2 weeks for cohorts using FOLFOX. For cohorts using CAPOX regimen, 130 mg/m^2 given every 3 weeks.
leucovorinDrug
200 (mFOLFOX7) or 400 (mFOLFOX6) mg/m^2 given IV every 2 weeks. Part of FOLFOX regimen.
fluorouracilDrug
400 mg/m^2 (IV bolus after leucovorin) and/or 2400 mg/m^2 (continuous infusion over 46 hours). Part of FOLFOX regimen.
capecitabineDrug
1000 mg/m^2 is taken twice per day orally on Days 1-14 of each 3 week cycle. Part of CAPOX regimen.
pembrolizumabDrug
Also called KEYTRUDA
400 mg given by IV on day 1 of cycle 1, then every 6 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1A | Experimental | Tucatinib + trastuzumab + FOLFOX given in 14-day cycles Receives: Drug: tucatinib; Drug: trastuzumab; Drug: oxaliplatin; Drug: leucovorin; Drug: fluorouracil |
| Cohort 1B | Experimental | Tucatinib + trastuzumab + FOLFOX given in 14-day cycles Receives: Drug: tucatinib; Drug: trastuzumab; Drug: oxaliplatin; Drug: leucovorin; Drug: fluorouracil |
| Cohort 1C | Experimental | Tucatinib + trastuzumab + CAPOX given in 21-day cycles Receives: Drug: tucatinib; Drug: trastuzumab; Drug: oxaliplatin; Drug: capecitabine |
| Cohort 1D | Experimental | Tucatinib + trastuzumab + FOLFOX. Tucatinib and FOLFOX given in 14-day cycles and trastuzumab given every 21 days Receives: Drug: tucatinib; Drug: trastuzumab; Drug: oxaliplatin; Drug: leucovorin; Drug: fluorouracil |
| Cohort 1E | Experimental | Tucatinib + trastuzumab + pembrolizumab + FOLFOX. Tucatinib and FOLFOX given in 14-day cycles, trastuzumab given in 21-day cycles, and pembrolizumab given in 42-day cycles Receives: Drug: tucatinib; Drug: trastuzumab; Drug: oxaliplatin; Drug: leucovorin; Drug: fluorouracil; Drug: pembrolizumab |
| Cohort 1F | Experimental | Tucatinib + trastuzumab + pembrolizumab + CAPOX. Tucatinib, trastuzumab, and CAPOX given in 21-day cycles and pembrolizumab given in 42-day cycles. Receives: Drug: tucatinib; Drug: trastuzumab; Drug: oxaliplatin; Drug: capecitabine; Drug: pembrolizumab |
| Cohort 1G | Experimental | Tucatinib + trastuzumab + pembrolizumab. Tucatinib and trastuzumab given in 21-day cycles and pembrolizumab given in 42-day cycles. Receives: Drug: tucatinib; Drug: trastuzumab; Drug: pembrolizumab |
| Cohort 2A | Experimental | Tucatinib + trastuzumab + pembrolizumab + (FOLFOX or CAPOX). Either (1) tucatinib and FOLFOX given in 14-day cycles or (2) tucatinib and CAPOX given in 21-day cycles. Trastuzumab given in 21-day cycles and pembrolizumab given in 42-day cycles. Receives: Drug: tucatinib; Drug: trastuzumab; Drug: oxaliplatin; Drug: leucovorin; Drug: fluorouracil; Drug: capecitabine; Drug: pembrolizumab |
| Cohort 2B | Experimental | Tucatinib + trastuzumab + FOLFOX given in 14-day cycles. Receives: Drug: tucatinib; Drug: trastuzumab; Drug: oxaliplatin; Drug: leucovorin; Drug: fluorouracil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Renal Dose-Limiting Toxicities (DLTs): Phase 1b (Cohort 1A and 1B)
A renal DLT was defined as an increase in serum cystatin C >1.5* baseline that was not related to pre-renal or post-renal etiologies (including disease progression, dehydration and intercurrent illness) and occurred during the period of treatment with tucatinib in combination with trastuzumab and FOLFOX between the first dose of tucatinib and the end of Cycle 3. Increased serum cystatin C for which there was an alternative clinical explanation (eg, clearly related to an intercurrent illness or disease progression) was not considered renal DLTs.
Measured: From first dose of tucatinib until end of Cycle 3 (up to 42 days)
Number of Participants With Treatment Emergent Adverse Events (TEAEs): Phase 1b (Cohort 1E and 1F)
An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil, oxaliplatin and pembrolizumab) through 30 days after the last dose of study treatment.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.7 months)
Number of Participants With Treatment Related TEAEs: Phase 1b (Cohort 1E and 1F)
An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil, oxaliplatin and pembrolizumab) through 30 days after the last dose of study treatment. Treatment related TEAEs were AEs related to any study treatment and relatedness was judged by investigator.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.7 months)
Number of Participants With Greater Than or Equal to (>=) Grade 3 TEAEs: Phase 1b (Cohort 1E and 1F)
An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil, oxaliplatin and pembrolizumab) through 30 days after the last dose of study treatment. TEAEs were graded according to National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI-CTCAE) version (v) 5.0 where grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening. Number of participants with >= grade 3 TEAEs are reported in this outcome measure.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.7 months)
Number of Participants With >= Grade 3 Treatment Related TEAEs: Phase 1b (Cohort 1E and 1F)
An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil, oxaliplatin and pembrolizumab) through 30 days after the last dose of study treatment. TEAEs were graded according to NCI-CTCAE v 5.0 where grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening. Treatment related TEAEs were AEs related to study treatment and relatedness was judged by investigator. Number of participants with >= grade 3 treatment related TEAEs are reported in this outcome measure.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.7 months)
Number of Participants With Any Serious Adverse Event (SAE): Phase 1b (Cohort 1E and 1F)
An SAE was any untoward medical occurrence at any dose that was fatal; life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was medically significant.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.7 months)
Number of Participants With Any Treatment Related SAE: Phase 1b (Cohort 1E and 1F)
An SAE was any untoward medical occurrence at any dose that was fatal; life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was medically significant. Treatment related SAEs were SAEs related to any study treatment and relatedness was judged by investigator.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.7 months)
Number of Participants With DLTs: Phase 1b (Cohort 1E)
DLTs were AEs/ laboratory abnormalities that were considered to be related to tucatinib/ tucatinib in combination with chemotherapy(mFOLFOX6/CAPOX) and/or trastuzumab and/or pembrolizumab. DLTs was defined any of following: a-)Hepatic- any instance of aspartate aminotransferase(AST)/ alanine aminotransferase(ALT)>3*upper limit of normal(ULN) and total bilirubin >2*ULN that is not thought to be due to progressive disease(PD)/other medical illness. PD:at least 20% increase in sum of diameters of target lesions,taking as reference smallest sum on study. In addition to relative increase of 20%,sum must also demonstrate an absolute increase of at least 5 millimeters(mm). b-) Non-hematologic- any clinically significant, non-hematologic treatment-related AE>= grade(G)3, with following exceptions:G3 fatigue=< 7days,G3 diarrhea,nausea/vomiting without optimal use of anti-emetics/antidiarrheals c-)hematologic:>=G3 febrile neutropenia and absolute neutrophil count(ANC) decreased G4 for >7days.
Measured: Cycle 1 (Up to 21 days)
Number of Participants With DLTs: Phase 1b (Cohort 1F)
DLTs were AEs/ laboratory abnormalities that were considered to be related to tucatinib/ tucatinib in combination with chemotherapy (mFOLFOX6/CAPOX) and/ or trastuzumab and/ or pembrolizumab. DLTs was defined any of following: a-) Hepatic- any instance of AST/ ALT >3*ULN and total bilirubin >2*ULN that is not thought to be due to PD/ other medical illness. PD: at least 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm. b-) Non-hematologic- any clinically significant, non-hematologic treatment-related AE>= grade 3, with following exceptions: grade 3 fatigue=< 7days, grade 3 diarrhea, nausea/vomiting without optimal use of anti-emetics/antidiarrheals c-) hematologic: >= grade 3 febrile neutropenia and ANC decreased grade 4 for >7days.
Measured: Cycle 1 (Up to 28 days)
Number of Participants With Treatment Emergent Hematological Laboratory Abnormalities: Phase 1b (Cohort 1E and 1F)
The following hematological parameters were assessed: hemoglobin decreased, leukocytes decreased, lymphocytes decreased, neutrophils decreased and platelets decreased. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil, oxaliplatin and pembrolizumab) through 30 days after the last dose of study treatment. Hematological laboratory abnormalities were graded according to NCI CTCAE v 5.0 (grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening). Participants with hematological abnormalities of any grade were reported.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.7 months)
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1E and 1F)
The following chemistry laboratory parameters were assessed: alanine aminotransferase (ALT) increased, albumin decreased, alkaline phosphatase increased, aspartate aminotransferase (AST) increased, calcium corrected for albumin decreased, creatinine increased, calcium corrected for albumin increased, lactate dehydrogenase increased, potassium decreased, potassium increased, sodium decreased, sodium increased and total bilirubin increased. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil, oxaliplatin and pembrolizumab) through 30 days after the last dose of study treatment Chemistry laboratory abnormalities were graded according to NCI CTCAE v 5.0 (grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening). Participants with chemistry abnormalities of any grade were reported.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.7 months)
Number of Participants With Clinically Significant Post-Baseline Vital Signs: Phase 1b (Cohort 1E and 1F)
Vital signs included temperature, blood pressure, heart rate and respiratory rate. Clinically significant vital signs were defined as: temperature greater than or equal to (>=) 38 degrees Celsius, respiratory rate greater than (>) 20 breaths per minute, systolic blood pressure (SBP) >= 120 millimeter of mercury (mmHg) or diastolic blood pressure (DBP) >= 80 mmHg, SBP >= 140 mmHg or DBP >= 90 mmHg and heart rate > 100 beats per minute (bpm).
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.7 months)
Number of Participants With TEAEs: Phase 1b (Cohort 1D)
An AE was defined as any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 21 months)
Number of Participants With Treatment Related TEAEs: Phase 1b (Cohort 1D)
An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. Treatment related TEAEs were AEs related to study treatment and relatedness was judged by investigator.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 21 months)
Number of Participants With >= Grade 3 TEAEs: Phase 1b (Cohort 1D)
An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. TEAEs were graded according to NCI-CTCAE v 5.0 where grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening. Number of participants with >= grade 3 TEAEs are reported in this outcome measure.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 21 months)
Number of Participants With >= Grade 3 Treatment Related TEAEs: Phase 1b (Cohort 1D)
An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. TEAEs were graded according to NCI-CTCAE v 5.0 where grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening. Treatment related TEAEs were AEs related to study treatment and relatedness was judged by investigator. Number of participants with >= grade 3 treatment related TEAEs are reported in this outcome measure.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 21 months)
Number of Participants With Any SAE: Phase 1b (Cohort 1D)
An SAE was any untoward medical occurrence at any dose that was fatal; life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was medically significant.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 21 months)
Number of Participants With Any Treatment Related SAE: Phase 1b (Cohort 1D)
An SAE was any untoward medical occurrence at any dose that was fatal; life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was medically significant. Treatment related SAEs were SAEs related to any study treatment and relatedness was judged by investigator.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 21 months)
Number of Participants With DLTs: Phase 1b (Cohort 1D)
DLTs were AEs/ laboratory abnormalities that were considered to be related to tucatinib/ tucatinib in combination with chemotherapy (mFOLFOX6/CAPOX) and/ or trastuzumab and/ or pembrolizumab. DLTs was defined any of following: a-) Hepatic- any instance of AST/ ALT >3*ULN and total bilirubin >2*ULN that is not thought to be due to PD/ other medical illness. PD: at least 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm. b-) Non-hematologic- any clinically significant, non-hematologic treatment-related AE>= grade 3, with following exceptions: grade 3 fatigue=< 7days, grade 3 diarrhea, nausea/vomiting without optimal use of anti-emetics/antidiarrheals c-) hematologic: >= grade 3 febrile neutropenia and ANC decreased grade 4 for >7days.
Measured: Cycle 1 (Up to 28 days)
Number of Participants With Treatment Emergent Hematological Laboratory Abnormalities: Phase 1b (Cohort 1D)
The following hematological parameters were assessed: hemoglobin decreased, leukocytes decreased, lymphocytes decreased, neutrophils decreased and platelets decreased. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. Hematological laboratory abnormalities were graded according to NCI CTCAE v 5.0 (grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening). Participants with hematological abnormalities of any grade were reported.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 21 months)
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1D)
The following chemistry parameters were assessed: ALT increased, albumin decreased, alkaline phosphatase increased, AST increased, calcium corrected for albumin decreased, creatinine increased, lactate dehydrogenase increased, potassium decreased, potassium increased, sodium decreased and sodium increased. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. Chemistry laboratory parameters abnormalities were graded according to NCI CTCAE v 5.0 (grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening). Participants with chemistry abnormalities of any grade were reported.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 21 months)
Number of Participants With Clinically Significant Post-Baseline Vital Signs: Phase 1b (Cohort 1D)
Vital signs included temperature, blood pressure, heart rate and respiratory rate. Clinically significant vital signs were defined as: temperature >= 38 degrees Celsius, respiratory rate > 20 breaths per minute, SBP >= 120 mmHg or DBP >= 80 mmHg, SBP >= 140 mmHg or DBP >= 90 mmHg and heart rate > 100 beats per minute (bpm).
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 21 months)
Number of Participants With TEAEs Leading to Dose Holds: Phase 1b (Cohort 1D)
An AE was defined as any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. Dose hold was considered as dose delay and dose elimination. Number of participants with TEAEs leading to dose holds are reported in this outcome measure.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 21 months)
Number of Participants With TEAEs Leading to Dose Reductions: Phase 1b (Cohort 1D)
An AE was defined as any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. Number of participants with TEAEs leading to dose reductions are reported in this outcome measure.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 21 months)
Number of Participants With TEAEs Leading to Dose Discontinuations: Phase 1b (Cohort 1D)
An AE was defined as any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. Number of participants with TEAEs leading to dose discontinuations (i.e. permanent withdrawal of tucatinib, trastuzumab, oxaliplatin, fluorouracil and leucovorin) are reported in this outcome measure.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 21 months)
Number of Participants With TEAEs: Phase 2 (Cohort 2B)
An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.9 months)
Number of Participants With Treatment Related TEAEs: Phase 2 (Cohort 2B)
An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. Treatment related TEAEs were AEs related to study treatment and relatedness was judged by investigator.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.9 months)
Number of Participants With >= Grade 3 TEAEs: Phase 2 (Cohort 2B)
An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. TEAEs were graded according to NCI-CTCAE v 5.0 (grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening). Number of participants with >= grade 3 TEAEs are reported in this outcome measure.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.9 months)
Number of Participants With >= Grade 3 Treatment Related TEAEs: Phase 2 (Cohort 2B)
An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. TEAEs were graded according to NCI-CTCAE v 5.0 (grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening). Treatment related TEAEs were AEs related to study treatment and relatedness was judged by investigator. Number of participants with >= grade 3 treatment related TEAEs are reported in this outcome measure.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.9 months)
Number of Participants With Any SAE: Phase 2 (Cohort 2B)
An SAE was any untoward medical occurrence at any dose that was fatal; life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was medically significant.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.9 months)
Number of Participants With Any Treatment Related SAE: Phase 2 (Cohort 2B)
An SAE was any untoward medical occurrence at any dose that was fatal; life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was medically significant. Treatment related SAEs were SAEs related to any study treatment and relatedness was judged by investigator.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.9 months)
Number of Participants With Treatment Emergent Hematological Laboratory Abnormalities: Phase 2 (Cohort 2B)
Following hematological parameters were assessed: hemoglobin decreased, leukocytes decreased, lymphocytes decreased, neutrophils decreased and platelets decreased. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. Hematological abnormalities were graded according to NCI CTCAE v 5.0; where, grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening). Participants with hematologic abnormalities of any grade were reported.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.9 months)
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 2 (Cohort 2B)
Following chemistry parameters were assessed: ALT increased, albumin decreased, alkaline phosphatase increased, AST increased, creatinine increased, glomerular filtration rate (GFR) estimated decreased, lactate dehydrogenase increased, potassium decreased, potassium increased, sodium decreased, sodium increased and total bilirubin increased. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. Chemistry abnormalities were graded according to NCI CTCAE v 5.0; where, grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening. Participants with chemistry abnormalities of any grade were reported.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.9 months)
Number of Participants With Clinically Significant Post-Baseline Vital Signs: Phase 2 (Cohort 2B)
Vital signs included temperature, blood pressure and heart rate. Clinically significant vital signs were defined as: temperature >= 38 degrees Celsius, respiratory rate > 20 breaths per minute, SBP >= 120 mmHg or DBP >= 80 mmHg, SBP >= 140 mmHg or DBP >= 90 mmHg and heart rate > 100 bpm.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.9 months)
Secondary outcomes (26)
Number of Participants With TEAEs: Phase 1b (Cohort 1A and 1B)
An AE was defined as any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 38.2 months)
Number of Participants With Treatment Related TEAEs: Phase 1b (Cohort 1A and 1B)
An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. Treatment related TEAEs were AEs related to study treatment and relatedness was judged by investigator.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 38.2 months)
Number of Participants With >= Grade 3 TEAEs: Phase 1b (Cohort 1A and 1B)
An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. TEAEs were graded according to NCI-CTCAE v 5.0 where grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening. Number of participants with >= grade 3 TEAEs are reported in this outcome measure.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 38.2 months)
Number of Participants With >= Grade 3 Treatment Related TEAEs: Phase 1b (Cohort 1A and 1B)
An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. TEAEs were graded according to NCI-CTCAE v 5.0 where grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening. Treatment related TEAEs were AEs related to study treatment and relatedness was judged by investigator. Number of participants with >= grade 3 treatment related TEAEs are reported in this outcome measure.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 38.2 months)
Number of Participants With Any SAE: Phase 1b (Cohort 1A and 1B)
An SAE was any untoward medical occurrence at any dose that was fatal; life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was medically significant.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 38.2 months)
Number of Participants With Any Treatment Related SAE: Phase 1b (Cohort 1A and 1B)
An SAE was any untoward medical occurrence at any dose that was fatal; life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was medically significant. Treatment related SAEs were SAEs related to any study treatment and relatedness was judged by investigator.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 38.2 months)
Number of Participants With Treatment Emergent Hematological Laboratory Abnormalities: Phase 1b (Cohort 1A and 1B)
Following hematological parameters were assessed: hemoglobin decreased, leukocytes decreased, lymphocytes decreased, neutrophils decreased and platelets decreased. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. Hematological laboratory abnormalities were graded according to NCI CTCAE v 5.0; where, grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening. Participants with hematological abnormalities of any grade were reported.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 38.2 months)
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1A and 1B)
Following chemistry parameters were assessed: ALT increased, albumin decreased, alkaline phosphatase increased, AST increased, calcium corrected for albumin decreased, calcium corrected for albumin increased, creatinine increased, Cystatin C increased, GFR estimated decreased, lactate dehydrogenase increased, potassium decreased, potassium increased, sodium decreased and total bilirubin increased. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. Chemistry laboratory abnormalities were graded according to NCI CTCAE v 5.0 grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening. Participants with chemistry abnormalities of any grade were reported.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 38.2 months)
Number of Participants With Clinically Significant Post-Baseline Vital Signs: Phase 1b (Cohort 1A and 1B)
Vital signs included temperature, blood pressure, heart rate and respiratory rate. Clinically significant vital signs were defined as: temperature >= 38 degrees Celsius, respiratory rate > 20 breaths per minute, SBP >= 120 mmHg or DBP >= 80 mmHg, SBP >= 140 mmHg or DBP >= 90 mmHg and heart rate > 100 bpm.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 38.2 months)
Change From Baseline in Glomerular Filtration Rate (GFR): Phase 1b (Cohort 1A and 1B)
GFR value was estimated using serum Cystatin C. Baseline was considered as the most recent non-missing measurement prior to the first dose of any study treatment.
Measured: Baseline, Cycle 1 Day 3, Cycle 1 Day 8, Cycle 2 Day 1, Cycle 2 Day 3, Cycle 2 Day 8 (each cycle=14 days)
Area Under the Plasma Concentration-Time Curve From 0 to 8 Hours (AUC 0-8h) of Tucatinib at Cycle 1 Day 1: Phase 1b (Cohort 1A and 1B)
PK parameters were determined using noncompartmental analysis.
Measured: Predose, 1 hour intra-dose, end of dose, 1, 2, 4, 6 hours after end of 2 hour oxaliplatin infusion (8 hours) on Day 1 of Cycle 1 and 2
Maximum Observed Concentration (Cmax) of Tucatinib: Phase 1b (Cohort 1A and 1B)
PK parameters were determined using noncompartmental analysis.
Measured: Predose, 1 hour intra-dose, end of dose, 1, 2, 4, 6 hours after end of 2 hour oxaliplatin infusion (8 hours) on Day 1 of Cycle 1 and 2
Observed Trough Concentration in Plasma (Ctrough) of Tucatinib: Phase 1b (Cohort 1A and 1B)
PK parameters were determined using noncompartmental analysis.
Measured: Predose on Day 1 of Cycle 2
Time at Which the Maximum Plasma Concentration Occurs (Tmax) of Tucatinib: Phase 1b (Cohort 1A and 1B)
PK parameters were determined using noncompartmental analysis.
Measured: Predose, 1 hour intra-dose, end of dose, 1, 2, 4, 6 hours after end of 2 hour oxaliplatin infusion (8 hours) on Day 1 of Cycle 1 and 2
AUC 0-8h of Oxaliplatin: Phase 1b (Cohort 1A and 1B)
PK parameters were determined using noncompartmental analysis.
Measured: Predose, 1 hour intra-dose, end of dose, 1, 2, 4, 6 hours after end of 2 hour oxaliplatin infusion (8 hours) on Day 1 of Cycle 1 and 2
Cmax of Oxaliplatin: Phase 1b (Cohort 1A and 1B)
PK parameters were determined using noncompartmental analysis.
Measured: Predose, 1 hour intra-dose, end of dose, 1, 2, 4, 6 hours after end of 2 hour oxaliplatin infusion (8 hours) on Day 1 of Cycle 1 and 2
Tmax of Oxaliplatin: Phase 1b (Cohort 1A and 1B)
PK parameters were determined using noncompartmental analysis.
Measured: Predose, 1 hour intra-dose, end of dose, 1, 2, 4, 6 hours after end of 2 hour oxaliplatin infusion (8 hours) on Day 1 of Cycle 1 and 2
Objective Response Rate (ORR) Per Investigator (INV): Phase 1b (Cohort 1E and 1F)
ORR was defined as percentage of participants with confirmed complete response (CR)/ partial response (PR) per investigator according to response evaluation criteria in solid tumors version 1.1 (RECIST) v1.1. For response to be considered confirmed, subsequent response had to be at least 4 weeks after initial response. CR: complete disappearance of all target lesions with exception of nodal disease and complete disappearance of non-target lesions and normalization of tumor marker level. Any pathological lymph nodes(whether target/ non-target) must have reduction in short axis to <10 mm. PR: >= 30% decrease in sum of diameters of target lesions, taking as reference baseline sum of diameters. 90% exact confidence interval (CI) was based on Clopper-Pearson method.
Measured: From the first dose of study treatment until the first documented CR or PR or before start of any new anti-cancer therapy (up to 24.1 months)
Duration of Response (DOR) Per INV: Phase 1b (Cohort 1E and 1F)
DOR was defined as time from first documented objective response (CR or PR that was subsequently confirmed) to first documented PD per RECIST v1.1 or death due to any cause, whichever occurred first. PD: at least a 20 % increase in sum of diameters of target lesions, taking as reference smallest sum on study (this included the baseline sum if that was the smallest on study). In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. CR: complete disappearance of all target lesions with exception of nodal disease and complete disappearance of non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: a >= 30 % decrease in sum of diameters of target lesions, taking as reference the baseline sum of diameters. 90% exact CI was based on Clopper-Pearson method.
Measured: From the first documented objective response until the first documentation of PD or death due to any cause, whichever occurred first (up to 18.1 months)
Progression Free Survival (PFS) Per INV: Phase 1b (Cohort 1E and 1F)
PFS as per INV was defined as time from the date of treatment initiation to date of documented PD as assessed by INV per RECIST version 1.1 or death from any cause, whichever occurred first. Participants without documentation of progression or death at the time of analysis were censored at the date of the last disease assessment. PD: at least 20 % increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions was also considered progression.
Measured: From the first dose of study treatment until the first documented PD or death from any cause or censoring date, whichever occurred first (up to 24.1 months)
Overall Survival (OS): Phase 1b (Cohort 1E and 1F)
OS was defined as the time from treatment initiation to death due to any cause. For a participant who was not known to have died by the end of study follow-up, observation of OS was censored on date the participant was last known to be alive (i.e., the date of last contact). Participants lacking data beyond the day of treatment initiation had their survival time censored on date of treatment initiation.
Measured: From date of start of study treatment until date of death or censoring date
Ctrough of Tucatinib: Phase 1b (Cohort 1E and 1F)
PK parameters were determined using noncompartmental analysis.
Measured: Predose on Day 1 of Cycle 2
Confirmed Objective Response Rate (cORR) Per INV: Phase 2 (Cohort 2B)
cORR was defined as the percentage of participants with a confirmed CR or PR per investigator according to RECIST v1.1. For a response to be considered confirmed, the subsequent response had to be at least 4 weeks after the initial response. CR: complete disappearance of all target lesions with exception of nodal disease and complete disappearance of non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: a >= 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. 90% exact CI was based on Clopper-Pearson method.
Measured: From the first dose of study treatment until the first documented CR or PR or before start of any new anti-cancer therapy (up to 20.9 months)
DOR Per INV: Phase 2 (Cohort 2B)
DOR was defined as time from first documented objective response (CR or PR that was subsequently confirmed) to first documented PD per RECIST v1.1 or death due to any cause, whichever occurred first. PD: at least a 20 % increase in sum of diameters of target lesions, taking as reference smallest sum on study (this included the baseline sum if that was the smallest on study). In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. CR: complete disappearance of all target lesions with exception of nodal disease and complete disappearance of non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: a >= 30 % decrease in sum of diameters of target lesions, taking as reference the baseline sum of diameters. 90% exact CI was based on Clopper-Pearson method.
Measured: From the first documented objective response until the first documentation of PD or death, whichever occurred first (up to 19.9 months)
PFS Per INV: Phase 2 (Cohort 2B)
PFS as per INV was defined as time from the date of treatment initiation to date of documented PD as assessed by INV per RECIST version 1.1 or death from any cause, whichever occurred first. Participants without documentation of progression or death at the time of analysis were censored at the date of the last disease assessment. PD: at least 20 % increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions was also considered progression.
Measured: From the first dose of study treatment until the first documented PD or death from any cause or censoring date, whichever occurred first (up to 20.9 months)
OS Per INV: Phase 2 (Cohort 2B)
OS was defined as the time from treatment initiation to death due to any cause. For a participant who was not known to have died by the end of study follow-up, observation of OS was censored on date the participant was last known to be alive (i.e., the date of last contact). Participants lacking data beyond the day of treatment initiation had their survival time censored on date of treatment initiation.
Measured: From date of start of study treatment until date of death or censoring date
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2020
- Study start15 Sep 2020
- Primary completion31 Jul 2024
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Colorectal CarcinomaStudies of the same condition, open and under way.
- More trials run by Seagen, a wholly owned subsidiary of PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seagen, a wholly owned subsidiary of Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04430738
- Sponsor's protocol ID
- SGNTUC-024
- Other IDs
- C4251005
- Status last verified
- Feb 2026
- First submitted
- 10 Jun 2020
- Last updated
- 24 Feb 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2 Dose Escalation and Expansion Study of Tucatinib in Combination With Trastuzumab and Oxaliplatin-based Chemotherapy or Pembrolizumab-containing Combinations for HER2+ Gastrointestinal Cancers
- ClinicalTrials.gov ID
- NCT04430738
- Acronym / sponsor ID
- SGNTUC-024
- Conditions
- Colorectal Carcinoma, Gastric Adenocarcinoma, GEJ Adenocarcinoma, Esophageal Adenocarcinoma, Cholangiocarcinoma, Gallbladder Carcinoma
- Keywords
- HER2+, HER2-positive, CRC, Gastric cancer, Esophageal cancer, Seattle Genetics
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Seagen, a wholly owned subsidiary of PfizerIndustry (pharma, biotech, devices)
- Study start
- 15 Sep 2020 (actual)
- Primary completion
- 31 Jul 2024 (actual)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 12 Jun 2020 (actual)
- Results
- Posted 9 Sep 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial studies tucatinib to find out if it is safe when given with trastuzumab and other anti-cancer drugs (pembrolizumab, FOLFOX, and CAPOX). It will look at what side effects happen when participants take this combination of drugs. A side effect is anything the drug does other than treating cancer. It will also look at whether tucatinib works with these drugs to treat certain types of cancer.
The participants in this trial have HER2-positive (HER2+) cancer in their gut, stomach, intestines, or gallbladder (gastrointestinal cancer).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| Cohort 1A | Experimental | Drug: tucatinib, Drug: trastuzumab, Drug: oxaliplatin, Drug: leucovorin, Drug: fluorouracilTucatinib + trastuzumab + FOLFOX given in 14-day cycles |
| Cohort 1B | Experimental | Drug: tucatinib, Drug: trastuzumab, Drug: oxaliplatin, Drug: leucovorin, Drug: fluorouracilTucatinib + trastuzumab + FOLFOX given in 14-day cycles |
| Cohort 1C | Experimental | Drug: tucatinib, Drug: trastuzumab, Drug: oxaliplatin, Drug: capecitabineTucatinib + trastuzumab + CAPOX given in 21-day cycles |
| Cohort 1D | Experimental | Drug: tucatinib, Drug: trastuzumab, Drug: oxaliplatin, Drug: leucovorin, Drug: fluorouracilTucatinib + trastuzumab + FOLFOX. Tucatinib and FOLFOX given in 14-day cycles and trastuzumab given every 21 days |
| Cohort 1E | Experimental | Drug: tucatinib, Drug: trastuzumab, Drug: oxaliplatin, Drug: leucovorin, Drug: fluorouracil, Drug: pembrolizumabTucatinib + trastuzumab + pembrolizumab + FOLFOX. Tucatinib and FOLFOX given in 14-day cycles, trastuzumab given in 21-day cycles, and pembrolizumab given in 42-day cycles |
| Cohort 1F | Experimental | Drug: tucatinib, Drug: trastuzumab, Drug: oxaliplatin, Drug: capecitabine, Drug: pembrolizumabTucatinib + trastuzumab + pembrolizumab + CAPOX. Tucatinib, trastuzumab, and CAPOX given in 21-day cycles and pembrolizumab given in 42-day cycles. |
| Cohort 1G | Experimental | Drug: tucatinib, Drug: trastuzumab, Drug: pembrolizumabTucatinib + trastuzumab + pembrolizumab. Tucatinib and trastuzumab given in 21-day cycles and pembrolizumab given in 42-day cycles. |
| Cohort 2A | Experimental | Drug: tucatinib, Drug: trastuzumab, Drug: oxaliplatin, Drug: leucovorin, Drug: fluorouracil, Drug: capecitabine, Drug: pembrolizumabTucatinib + trastuzumab + pembrolizumab + (FOLFOX or CAPOX). Either (1) tucatinib and FOLFOX given in 14-day cycles or (2) tucatinib and CAPOX given in 21-day cycles. Trastuzumab given in 21-day cycles and pembrolizumab given in 42-day cycles. |
| Cohort 2B | Experimental | Drug: tucatinib, Drug: trastuzumab, Drug: oxaliplatin, Drug: leucovorin, Drug: fluorouracilTucatinib + trastuzumab + FOLFOX given in 14-day cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Participants must have an unresectable or metastatic solid malignancy that is histologically or cytologically confirmed to be one of the tumor types listed below:
- Participants must be candidates to receive an oxaliplatin-based regimen as part of their standard-of-care treatment for all cohorts, except Cohort 1G.
- HER2+ disease, as determined by historic or local laboratory testing
- Phase 1b cohorts: measurable or non-measurable disease according to RECIST v1.1 as determined by the investigator
- Phase 2 cohorts: measurable disease according to RECIST v1.1 as determined by the investigator
Key exclusion criteria (5 listed)
- History of known hypersensitivity to planned study treatment
- Known to be positive for Hepatitis B or C
- For Cohorts 2A and 2B: prior anti-HER2 therapies
- For Cohorts 1E, 1F, 1G, 2A: Prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137), and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event (irAE)
- There are additional inclusion criteria. The study center will determine if criteria for participations are met.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| tucatinibAlso: TUKYSAFor Cohort 1A, 150 mg will be administered twice daily by mouth (orally) from Cycle 1 Day 8 onwards. For all other cohorts, 300 mg (or intermediate dose) will be given orally twice daily starting on Cycle 1 Day 1. | Drug | Cohort 1A, Cohort 1B, Cohort 1C, Cohort 1D, Cohort 1E, Cohort 1F, Cohort 1G, Cohort 2A, Cohort 2B |
| trastuzumabCohorts 1A and 1B: a 6 mg/kg loading dose will be given into the vein (IV; intravenously) on Cycle 1 Day 1, followed by a dose of 4 mg/kg IV every 2 weeks starting on Cycle 2 Day 1. Cohorts 1C, 1D, 1E, 1F, 1G, 2A, and 2B: an 8 mg/kg loading dose will be administered IV on Cycle 1 Day 1, followed by a dose of 6 mg/kg IV every 3 weeks thereafter. | Drug | Cohort 1A, Cohort 1B, Cohort 1C, Cohort 1D, Cohort 1E, Cohort 1F, Cohort 1G, Cohort 2A, Cohort 2B |
| oxaliplatin85 mg/m^2 given IV every 2 weeks for cohorts using FOLFOX. For cohorts using CAPOX regimen, 130 mg/m^2 given every 3 weeks. | Drug | Cohort 1A, Cohort 1B, Cohort 1C, Cohort 1D, Cohort 1E, Cohort 1F, Cohort 2A, Cohort 2B |
| leucovorin200 (mFOLFOX7) or 400 (mFOLFOX6) mg/m^2 given IV every 2 weeks. Part of FOLFOX regimen. | Drug | Cohort 1A, Cohort 1B, Cohort 1D, Cohort 1E, Cohort 2A, Cohort 2B |
| fluorouracil400 mg/m^2 (IV bolus after leucovorin) and/or 2400 mg/m^2 (continuous infusion over 46 hours). Part of FOLFOX regimen. | Drug | Cohort 1A, Cohort 1B, Cohort 1D, Cohort 1E, Cohort 2A, Cohort 2B |
| capecitabine1000 mg/m^2 is taken twice per day orally on Days 1-14 of each 3 week cycle. Part of CAPOX regimen. | Drug | Cohort 1C, Cohort 1F, Cohort 2A |
| pembrolizumabAlso: KEYTRUDA400 mg given by IV on day 1 of cycle 1, then every 6 weeks. | Drug | Cohort 1E, Cohort 1F, Cohort 1G, Cohort 2A |
Primary outcome
Number of Participants With Renal Dose-Limiting Toxicities (DLTs): Phase 1b (Cohort 1A and 1B)
Time frame: From first dose of tucatinib until end of Cycle 3 (up to 42 days)
A renal DLT was defined as an increase in serum cystatin C >1.5* baseline that was not related to pre-renal or post-renal etiologies (including disease progression, dehydration and intercurrent illness) and occurred during the period of treatment with tucatinib in combination with trastuzumab and FOLFOX between the first dose of tucatinib and the end of Cycle 3. Increased serum cystatin C for which there was an alternative clinical explanation (eg, clearly related to an intercurrent illness or disease progression) was not considered renal DLTs.
Number of Participants With Treatment Emergent Adverse Events (TEAEs): Phase 1b (Cohort 1E and 1F)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.7 months)
An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil, oxaliplatin and pembrolizumab) through 30 days after the last dose of study treatment.
Number of Participants With Treatment Related TEAEs: Phase 1b (Cohort 1E and 1F)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.7 months)
An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil, oxaliplatin and pembrolizumab) through 30 days after the last dose of study treatment. Treatment related TEAEs were AEs related to any study treatment and relatedness was judged by investigator.
Number of Participants With Greater Than or Equal to (>=) Grade 3 TEAEs: Phase 1b (Cohort 1E and 1F)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.7 months)
An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil, oxaliplatin and pembrolizumab) through 30 days after the last dose of study treatment. TEAEs were graded according to National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI-CTCAE) version (v) 5.0 where grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening. Number of participants with >= grade 3 TEAEs are reported in this outcome measure.
Number of Participants With >= Grade 3 Treatment Related TEAEs: Phase 1b (Cohort 1E and 1F)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.7 months)
An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil, oxaliplatin and pembrolizumab) through 30 days after the last dose of study treatment. TEAEs were graded according to NCI-CTCAE v 5.0 where grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening. Treatment related TEAEs were AEs related to study treatment and relatedness was judged by investigator. Number of participants with >= grade 3 treatment related TEAEs are reported in this outcome measure.
Number of Participants With Any Serious Adverse Event (SAE): Phase 1b (Cohort 1E and 1F)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.7 months)
An SAE was any untoward medical occurrence at any dose that was fatal; life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was medically significant.
Number of Participants With Any Treatment Related SAE: Phase 1b (Cohort 1E and 1F)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.7 months)
An SAE was any untoward medical occurrence at any dose that was fatal; life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was medically significant. Treatment related SAEs were SAEs related to any study treatment and relatedness was judged by investigator.
Number of Participants With DLTs: Phase 1b (Cohort 1E)
Time frame: Cycle 1 (Up to 21 days)
DLTs were AEs/ laboratory abnormalities that were considered to be related to tucatinib/ tucatinib in combination with chemotherapy(mFOLFOX6/CAPOX) and/or trastuzumab and/or pembrolizumab. DLTs was defined any of following: a-)Hepatic- any instance of aspartate aminotransferase(AST)/ alanine aminotransferase(ALT)>3*upper limit of normal(ULN) and total bilirubin >2*ULN that is not thought to be due to progressive disease(PD)/other medical illness. PD:at least 20% increase in sum of diameters of target lesions,taking as reference smallest sum on study. In addition to relative increase of 20%,sum must also demonstrate an absolute increase of at least 5 millimeters(mm). b-) Non-hematologic- any clinically significant, non-hematologic treatment-related AE>= grade(G)3, with following exceptions:G3 fatigue=< 7days,G3 diarrhea,nausea/vomiting without optimal use of anti-emetics/antidiarrheals c-)hematologic:>=G3 febrile neutropenia and absolute neutrophil count(ANC) decreased G4 for >7days.
Number of Participants With DLTs: Phase 1b (Cohort 1F)
Time frame: Cycle 1 (Up to 28 days)
DLTs were AEs/ laboratory abnormalities that were considered to be related to tucatinib/ tucatinib in combination with chemotherapy (mFOLFOX6/CAPOX) and/ or trastuzumab and/ or pembrolizumab. DLTs was defined any of following: a-) Hepatic- any instance of AST/ ALT >3*ULN and total bilirubin >2*ULN that is not thought to be due to PD/ other medical illness. PD: at least 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm. b-) Non-hematologic- any clinically significant, non-hematologic treatment-related AE>= grade 3, with following exceptions: grade 3 fatigue=< 7days, grade 3 diarrhea, nausea/vomiting without optimal use of anti-emetics/antidiarrheals c-) hematologic: >= grade 3 febrile neutropenia and ANC decreased grade 4 for >7days.
Number of Participants With Treatment Emergent Hematological Laboratory Abnormalities: Phase 1b (Cohort 1E and 1F)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.7 months)
The following hematological parameters were assessed: hemoglobin decreased, leukocytes decreased, lymphocytes decreased, neutrophils decreased and platelets decreased. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil, oxaliplatin and pembrolizumab) through 30 days after the last dose of study treatment. Hematological laboratory abnormalities were graded according to NCI CTCAE v 5.0 (grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening). Participants with hematological abnormalities of any grade were reported.
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1E and 1F)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.7 months)
The following chemistry laboratory parameters were assessed: alanine aminotransferase (ALT) increased, albumin decreased, alkaline phosphatase increased, aspartate aminotransferase (AST) increased, calcium corrected for albumin decreased, creatinine increased, calcium corrected for albumin increased, lactate dehydrogenase increased, potassium decreased, potassium increased, sodium decreased, sodium increased and total bilirubin increased. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil, oxaliplatin and pembrolizumab) through 30 days after the last dose of study treatment Chemistry laboratory abnormalities were graded according to NCI CTCAE v 5.0 (grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening). Participants with chemistry abnormalities of any grade were reported.
Number of Participants With Clinically Significant Post-Baseline Vital Signs: Phase 1b (Cohort 1E and 1F)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.7 months)
Vital signs included temperature, blood pressure, heart rate and respiratory rate. Clinically significant vital signs were defined as: temperature greater than or equal to (>=) 38 degrees Celsius, respiratory rate greater than (>) 20 breaths per minute, systolic blood pressure (SBP) >= 120 millimeter of mercury (mmHg) or diastolic blood pressure (DBP) >= 80 mmHg, SBP >= 140 mmHg or DBP >= 90 mmHg and heart rate > 100 beats per minute (bpm).
Number of Participants With TEAEs: Phase 1b (Cohort 1D)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 21 months)
An AE was defined as any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment.
Number of Participants With Treatment Related TEAEs: Phase 1b (Cohort 1D)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 21 months)
An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. Treatment related TEAEs were AEs related to study treatment and relatedness was judged by investigator.
Number of Participants With >= Grade 3 TEAEs: Phase 1b (Cohort 1D)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 21 months)
An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. TEAEs were graded according to NCI-CTCAE v 5.0 where grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening. Number of participants with >= grade 3 TEAEs are reported in this outcome measure.
Number of Participants With >= Grade 3 Treatment Related TEAEs: Phase 1b (Cohort 1D)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 21 months)
An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. TEAEs were graded according to NCI-CTCAE v 5.0 where grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening. Treatment related TEAEs were AEs related to study treatment and relatedness was judged by investigator. Number of participants with >= grade 3 treatment related TEAEs are reported in this outcome measure.
Number of Participants With Any SAE: Phase 1b (Cohort 1D)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 21 months)
An SAE was any untoward medical occurrence at any dose that was fatal; life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was medically significant.
Number of Participants With Any Treatment Related SAE: Phase 1b (Cohort 1D)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 21 months)
An SAE was any untoward medical occurrence at any dose that was fatal; life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was medically significant. Treatment related SAEs were SAEs related to any study treatment and relatedness was judged by investigator.
Number of Participants With DLTs: Phase 1b (Cohort 1D)
Time frame: Cycle 1 (Up to 28 days)
DLTs were AEs/ laboratory abnormalities that were considered to be related to tucatinib/ tucatinib in combination with chemotherapy (mFOLFOX6/CAPOX) and/ or trastuzumab and/ or pembrolizumab. DLTs was defined any of following: a-) Hepatic- any instance of AST/ ALT >3*ULN and total bilirubin >2*ULN that is not thought to be due to PD/ other medical illness. PD: at least 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm. b-) Non-hematologic- any clinically significant, non-hematologic treatment-related AE>= grade 3, with following exceptions: grade 3 fatigue=< 7days, grade 3 diarrhea, nausea/vomiting without optimal use of anti-emetics/antidiarrheals c-) hematologic: >= grade 3 febrile neutropenia and ANC decreased grade 4 for >7days.
Number of Participants With Treatment Emergent Hematological Laboratory Abnormalities: Phase 1b (Cohort 1D)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 21 months)
The following hematological parameters were assessed: hemoglobin decreased, leukocytes decreased, lymphocytes decreased, neutrophils decreased and platelets decreased. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. Hematological laboratory abnormalities were graded according to NCI CTCAE v 5.0 (grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening). Participants with hematological abnormalities of any grade were reported.
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1D)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 21 months)
The following chemistry parameters were assessed: ALT increased, albumin decreased, alkaline phosphatase increased, AST increased, calcium corrected for albumin decreased, creatinine increased, lactate dehydrogenase increased, potassium decreased, potassium increased, sodium decreased and sodium increased. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. Chemistry laboratory parameters abnormalities were graded according to NCI CTCAE v 5.0 (grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening). Participants with chemistry abnormalities of any grade were reported.
Number of Participants With Clinically Significant Post-Baseline Vital Signs: Phase 1b (Cohort 1D)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 21 months)
Vital signs included temperature, blood pressure, heart rate and respiratory rate. Clinically significant vital signs were defined as: temperature >= 38 degrees Celsius, respiratory rate > 20 breaths per minute, SBP >= 120 mmHg or DBP >= 80 mmHg, SBP >= 140 mmHg or DBP >= 90 mmHg and heart rate > 100 beats per minute (bpm).
Number of Participants With TEAEs Leading to Dose Holds: Phase 1b (Cohort 1D)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 21 months)
An AE was defined as any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. Dose hold was considered as dose delay and dose elimination. Number of participants with TEAEs leading to dose holds are reported in this outcome measure.
Number of Participants With TEAEs Leading to Dose Reductions: Phase 1b (Cohort 1D)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 21 months)
An AE was defined as any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. Number of participants with TEAEs leading to dose reductions are reported in this outcome measure.
Number of Participants With TEAEs Leading to Dose Discontinuations: Phase 1b (Cohort 1D)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 21 months)
An AE was defined as any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. Number of participants with TEAEs leading to dose discontinuations (i.e. permanent withdrawal of tucatinib, trastuzumab, oxaliplatin, fluorouracil and leucovorin) are reported in this outcome measure.
Number of Participants With TEAEs: Phase 2 (Cohort 2B)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.9 months)
An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment.
Number of Participants With Treatment Related TEAEs: Phase 2 (Cohort 2B)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.9 months)
An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. Treatment related TEAEs were AEs related to study treatment and relatedness was judged by investigator.
Number of Participants With >= Grade 3 TEAEs: Phase 2 (Cohort 2B)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.9 months)
An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. TEAEs were graded according to NCI-CTCAE v 5.0 (grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening). Number of participants with >= grade 3 TEAEs are reported in this outcome measure.
Number of Participants With >= Grade 3 Treatment Related TEAEs: Phase 2 (Cohort 2B)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.9 months)
An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. TEAEs were graded according to NCI-CTCAE v 5.0 (grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening). Treatment related TEAEs were AEs related to study treatment and relatedness was judged by investigator. Number of participants with >= grade 3 treatment related TEAEs are reported in this outcome measure.
Number of Participants With Any SAE: Phase 2 (Cohort 2B)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.9 months)
An SAE was any untoward medical occurrence at any dose that was fatal; life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was medically significant.
Number of Participants With Any Treatment Related SAE: Phase 2 (Cohort 2B)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.9 months)
An SAE was any untoward medical occurrence at any dose that was fatal; life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was medically significant. Treatment related SAEs were SAEs related to any study treatment and relatedness was judged by investigator.
Number of Participants With Treatment Emergent Hematological Laboratory Abnormalities: Phase 2 (Cohort 2B)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.9 months)
Following hematological parameters were assessed: hemoglobin decreased, leukocytes decreased, lymphocytes decreased, neutrophils decreased and platelets decreased. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. Hematological abnormalities were graded according to NCI CTCAE v 5.0; where, grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening). Participants with hematologic abnormalities of any grade were reported.
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 2 (Cohort 2B)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.9 months)
Following chemistry parameters were assessed: ALT increased, albumin decreased, alkaline phosphatase increased, AST increased, creatinine increased, glomerular filtration rate (GFR) estimated decreased, lactate dehydrogenase increased, potassium decreased, potassium increased, sodium decreased, sodium increased and total bilirubin increased. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, leucovorin, fluorouracil and oxaliplatin) through 30 days after the last dose of study treatment. Chemistry abnormalities were graded according to NCI CTCAE v 5.0; where, grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening. Participants with chemistry abnormalities of any grade were reported.
Number of Participants With Clinically Significant Post-Baseline Vital Signs: Phase 2 (Cohort 2B)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 20.9 months)
Vital signs included temperature, blood pressure and heart rate. Clinically significant vital signs were defined as: temperature >= 38 degrees Celsius, respiratory rate > 20 breaths per minute, SBP >= 120 mmHg or DBP >= 80 mmHg, SBP >= 140 mmHg or DBP >= 90 mmHg and heart rate > 100 bpm.
26 secondary outcomes
Number of Participants With TEAEs: Phase 1b (Cohort 1A and 1B)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 38.2 months)
Number of Participants With Treatment Related TEAEs: Phase 1b (Cohort 1A and 1B)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 38.2 months)
Number of Participants With >= Grade 3 TEAEs: Phase 1b (Cohort 1A and 1B)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 38.2 months)
Number of Participants With >= Grade 3 Treatment Related TEAEs: Phase 1b (Cohort 1A and 1B)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 38.2 months)
Number of Participants With Any SAE: Phase 1b (Cohort 1A and 1B)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 38.2 months)
Number of Participants With Any Treatment Related SAE: Phase 1b (Cohort 1A and 1B)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 38.2 months)
Number of Participants With Treatment Emergent Hematological Laboratory Abnormalities: Phase 1b (Cohort 1A and 1B)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 38.2 months)
Number of Participants With Treatment Emergent Chemistry Laboratory Abnormalities: Phase 1b (Cohort 1A and 1B)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 38.2 months)
Number of Participants With Clinically Significant Post-Baseline Vital Signs: Phase 1b (Cohort 1A and 1B)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment, end of study date, death date, or data cutoff date, whichever was earlier (maximum of 38.2 months)
Change From Baseline in Glomerular Filtration Rate (GFR): Phase 1b (Cohort 1A and 1B)
Time frame: Baseline, Cycle 1 Day 3, Cycle 1 Day 8, Cycle 2 Day 1, Cycle 2 Day 3, Cycle 2 Day 8 (each cycle=14 days)
Area Under the Plasma Concentration-Time Curve From 0 to 8 Hours (AUC 0-8h) of Tucatinib at Cycle 1 Day 1: Phase 1b (Cohort 1A and 1B)
Time frame: Predose, 1 hour intra-dose, end of dose, 1, 2, 4, 6 hours after end of 2 hour oxaliplatin infusion (8 hours) on Day 1 of Cycle 1 and 2
Maximum Observed Concentration (Cmax) of Tucatinib: Phase 1b (Cohort 1A and 1B)
Time frame: Predose, 1 hour intra-dose, end of dose, 1, 2, 4, 6 hours after end of 2 hour oxaliplatin infusion (8 hours) on Day 1 of Cycle 1 and 2
Observed Trough Concentration in Plasma (Ctrough) of Tucatinib: Phase 1b (Cohort 1A and 1B)
Time frame: Predose on Day 1 of Cycle 2
Time at Which the Maximum Plasma Concentration Occurs (Tmax) of Tucatinib: Phase 1b (Cohort 1A and 1B)
Time frame: Predose, 1 hour intra-dose, end of dose, 1, 2, 4, 6 hours after end of 2 hour oxaliplatin infusion (8 hours) on Day 1 of Cycle 1 and 2
AUC 0-8h of Oxaliplatin: Phase 1b (Cohort 1A and 1B)
Time frame: Predose, 1 hour intra-dose, end of dose, 1, 2, 4, 6 hours after end of 2 hour oxaliplatin infusion (8 hours) on Day 1 of Cycle 1 and 2
Cmax of Oxaliplatin: Phase 1b (Cohort 1A and 1B)
Time frame: Predose, 1 hour intra-dose, end of dose, 1, 2, 4, 6 hours after end of 2 hour oxaliplatin infusion (8 hours) on Day 1 of Cycle 1 and 2
Tmax of Oxaliplatin: Phase 1b (Cohort 1A and 1B)
Time frame: Predose, 1 hour intra-dose, end of dose, 1, 2, 4, 6 hours after end of 2 hour oxaliplatin infusion (8 hours) on Day 1 of Cycle 1 and 2
Objective Response Rate (ORR) Per Investigator (INV): Phase 1b (Cohort 1E and 1F)
Time frame: From the first dose of study treatment until the first documented CR or PR or before start of any new anti-cancer therapy (up to 24.1 months)
Duration of Response (DOR) Per INV: Phase 1b (Cohort 1E and 1F)
Time frame: From the first documented objective response until the first documentation of PD or death due to any cause, whichever occurred first (up to 18.1 months)
Progression Free Survival (PFS) Per INV: Phase 1b (Cohort 1E and 1F)
Time frame: From the first dose of study treatment until the first documented PD or death from any cause or censoring date, whichever occurred first (up to 24.1 months)
Overall Survival (OS): Phase 1b (Cohort 1E and 1F)
Time frame: From date of start of study treatment until date of death or censoring date
Ctrough of Tucatinib: Phase 1b (Cohort 1E and 1F)
Time frame: Predose on Day 1 of Cycle 2
Confirmed Objective Response Rate (cORR) Per INV: Phase 2 (Cohort 2B)
Time frame: From the first dose of study treatment until the first documented CR or PR or before start of any new anti-cancer therapy (up to 20.9 months)
DOR Per INV: Phase 2 (Cohort 2B)
Time frame: From the first documented objective response until the first documentation of PD or death, whichever occurred first (up to 19.9 months)
PFS Per INV: Phase 2 (Cohort 2B)
Time frame: From the first dose of study treatment until the first documented PD or death from any cause or censoring date, whichever occurred first (up to 20.9 months)
OS Per INV: Phase 2 (Cohort 2B)
Time frame: From date of start of study treatment until date of death or censoring date
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
27 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing tucatinib, trastuzumab and oxaliplatin in people with Colorectal Carcinoma and Gastric Adenocarcinoma, run by Seagen, a wholly owned subsidiary of Pfizer at 27 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 24 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in United States, Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Sep 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Renal Dose-Limiting Toxicities (DLTs): Phase 1b (Cohort 1A and 1B) (time frame: From first dose of tucatinib until end of Cycle 3 (up to 42 days)). The study lists 34 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2026.