Metastatic Colorectal CancerPhase 2NCT04479436
A Study to Evaluate U3-1402 in Subjects With Advanced or Metastatic Colorectal Cancer
A Phase 2 study testing Patritumab Deruxtecan in people with Metastatic Colorectal Cancer, run by Daiichi Sankyo at 46 sites in 8 countries.
Trial summary
This study is designed to primarily evaluate the safety and efficacy of U3-1402 in participants with advanced or metastatic colorectal cancer (CRC) who have received at least 2 prior lines of therapy and will explore clinical benefit according to human epidermal growth factor receptor 3 (HER3) tumor expression level… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Patritumab Deruxtecan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 46 sitesin 8 countries
- Study dates
- 14 Sep 2020to 3 Feb 2022
- 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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant has provided written informed consent prior to the start of any study specific procedures.
- Participants ≥18 years (follow local regulatory requirements if the legal age of consent for study participation is >18 years old).
- Pathological/histological confirmation of advanced or metastatic colon or rectal adenocarcinoma.
- Must be resistant, refractory, or intolerant to at least 2 prior lines of systemic therapy, that must include all of the following agents:
- Fluoropyrimidine
- Irinotecan
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- Platinum agents (e.g, oxaliplatin)
- An anti-epidermal growth factor receptor (EGFR) agent, if clinically indicated
- An anti-VEGF agent, if clinically indicated (eg, bevacizumab)
- An immune checkpoint inhibitor (eg, microsatellite instability-high [MSI-H] status)
- A BRAF inhibitor, if clinically indicated (eg, BRAF V600E positive)
- Has at least 1 measurable lesion confirmed by blinded independent central review (BICR) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1.
- Willing to provide a required pre-treatment tumor biopsy and an additional archival tissue sample for the assessment of HER3 expression levels by immunohistochemistry and exploratory biomarkers, defined as:
- Pre-treatment tumor biopsy. Participants may be exempted from the requirement to provide a pre-treatment tumor biopsy if archival tumor tissue was collected within 3 months of screening during or after treatment with the last prior cancer treatment and is of sufficient quantity (2 cores or 20 slides with adequate tumor tissue content).
- An additional archival tissue sample collected greater than 3 months prior to screening must be available and of sufficient quantity, as defined above, at the time of screening. If an archival tissue sample (collected greater than 3 months prior to screening) is not available, a subject may be included provided the pre-treatment tumor biopsy is obtained and after discussion and agreement from Sponsor (Medical Monitor or designee).
- Consent to provide on-treatment tumor biopsy. When at least 10 treatment tumor biopsies have been collected, the Sponsor will provide written notification of a change to the requirement.
- Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
- Life expectancy ≥3 months.
- Has adequate bone marrow reserve and organ function at baseline based on local laboratory data defined as follows within 14 days prior to Cycle 1 Day 1:
- Platelet count: ≥100,000/mm^3 or ≥100 × 10^9/L (platelet transfusions are not allowed up to 14 days prior to Cycle 1 Day 1 to meet eligibility)
- Hemoglobin: ≥9.0 g/dL (transfusion and/or growth factor support is allowed)
- Absolute neutrophil count: ≥1500/mm^3 or ≥1.5 × 10^9/L
- Serum creatinine (SCr) OR creatinine clearance (CrCl): SCr ≤ 1.5 × upper limit of normal (ULN), OR CrCl ≥ 30 mL/min as calculated using the Cockcroft- Gault equation or measured CrCl; confirmation of CrCl is only required when creatinine is >1.5 × ULN
- Alanine aminotransferase /aspartate aminotransferase: ≤3 × ULN (if liver metastases are present, ≤5 × ULN)
- Total bilirubin: ≤1.5 × ULN if no liver metastases (<3 × ULN in the presence of documented Gilbert's syndrome [unconjugated hyperbilirubinemia] or liver metastases)
- Serum albumin: ≥2.5 g/dL
- Prothrombin time (PT) or PT-international normalized ratio (INR) and activated partial thromboplastin time (aPTT) / partial thromboplastin time (PTT): ≤1.5 × ULN except for subjects on coumarin- derivative anticoagulants or other similar anticoagulant therapy, who must have PT-INR within therapeutic range as deemed appropriate by the Investigator
Who cannot join
- Any history of interstitial lung disease (including pulmonary fibrosis or radiation pneumonitis), has current interstitial lung disease (ILD), or is suspected to have such disease by imaging during screening.
- Clinically severe pulmonary compromise (based on Investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to:
- any underlying pulmonary disorder (e.g., pulmonary emboli, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion)
- any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement (eg, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis)
- OR prior complete pneumonectomy.
- Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to Cycle 1 Day 1. Participants who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the study.
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- Evidence of leptomeningeal disease.
- Evidence of clinically active spinal cord compression or brain metastases
- Inadequate washout period prior to Cycle 1 Day 1 of U3-1402:
- Whole brain radiation therapy <14 days or stereotactic brain radiation therapy <7 days;
- Any cytotoxic chemotherapy, investigational agent or other anticancer drug(s) from a previous cancer treatment regimen or clinical study <14 days or 5 half-lives, whichever is longer;
- Monoclonal antibodies other than immune checkpoint inhibitors, such as bevacizumab (anti-VEGF) and cetuximab (anti-EGFRs) <28 days;
- Immune checkpoint inhibitor therapy <21 days;
- Major surgery (excluding placement of vascular access) <4 weeks;
- Radiotherapy treatment to >30% of the bone marrow or with a wide field of radiation <28 days or palliative radiation therapy <14 days;
- Chloroquine/hydroxychloroquine ≤14 days.
- Prior treatment with an anti-HER3 antibody and/or antibody drug conjugate (ADC) that consists of an exatecan derivative that is any topoisomerase I inhibitor (e.g, trastuzumab deruxtecan).
- Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 Grade ≤1 or baseline.
- Had primary malignancies other than CRC within 3 years prior to Cycle 1 Day 1, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated.
- Uncontrolled or significant cardiovascular disease prior to Cycle 1 Day 1.
- Known Hepatitis B and/or Hepatitis C infection, such as those with serologic evidence of viral infection within 28 days of Cycle 1 Day 1.
- Participants with past or resolved hepatitis B virus (HBV) infection are eligible if:
- Hepatitis B surface antigen (HBsAg) negative and hepatitis B core antibody (anti-HBc) positive; OR
- HBsAg positive and HBV deoxyribonucleic acid (DNA) viral load is documented to be ≤2000 IU/mL in the absence of anti-viral therapy and during the previous 12 weeks prior to the viral load evaluation with normal transaminases values (in the absence of liver metastasis); OR
- HBsAg positive and HBV DNA viral load is documented to be ≤2000 IU/mL in the absence of anti-viral therapy and during the previous 12 weeks prior to the viral load evaluation for participants with liver metastasis and abnormal transaminases with a result of AST/ALT <3 × ULN.
- Participants with a history of hepatitis C infection will be eligible for enrollment only if the viral load according to local standards of detection is documented to be below the level of detection in the absence of anti-viral therapy during the previous 12 weeks (ie, sustained viral response according to the local product label but no less than 12 weeks, whichever is longer).
- Participant with any human immunodeficiency virus (HIV) infection.
- Any evidence of severe or uncontrolled systemic diseases (including active bleeding diatheses, active infection), psychiatric illness/social situations, geographical factors, substance abuse, or other factors which in the Investigator's opinion makes it undesirable for the participant to participate in the study or which would jeopardize compliance with the protocol. Screening for chronic conditions is not required.
Trial locations and contacts
46 sites in 8 countries.
46 sites in 8 countries
United States21 sites
Emory University
Atlanta, Georgia, 30322
University of Colorado Hospital
Aurora, Colorado, 80045
John Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21287
Northwestern Medical Faculty Foundation NMFF Hematology Oncology
Chicago, Illinois, 60611
Mary Crowley Cancer Research
Dallas, Texas, 75230
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Henry Ford Health System
Detroit, Michigan, 48202
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
Duke University Medical Center
Durham, North Carolina, 27710
Virgina Cancer Specialists
Fairfax, Virginia, 22031
Highlands Oncology
Fayetteville, Arkansas, 72703
West Cancer Center
Germantown, Tennessee, 38138
MD Anderson Cancer Center University of Texas
Houston, Texas, 77030
Sarah Cannon
Nashville, Tennessee, 37203
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08901
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Nebraska Cancer Specialists
Omaha, Nebraska, 68130
Mayo Clinic
Rochester, Minnesota, 55902
Utah Cancer Specialists
Salt Lake City, Utah, 84106
Washington University
St Louis, Missouri, 63110
Moffitt Cancer Center
Tampa, Florida, 33612
Spain6 sites
Hospital del Mar - Institut Hospital del Mar d'Investigacions Mediques IMIM
Barcelona, 08003
VHIO Valle de Hebron Instituto de Oncologia
Barcelona, 08035
Hospital Universitario La Paz
Madrid, 28046
Hospital Universitario HM Sanchinarro, CIOCC
Madrid, 28050
Consorci Corporació Sanitària Parc Taulí de Sabadell
Sabadell, 08208
Hospital Universitario Virgen del Rocio
Seville, 41013
Japan5 sites
National Cancer Center Hospital East
Chiba, 277-0023
Aichi Cancer Center Hospital
Nagoya, Nagoya-shi, Aichi-ken, 464-8681
National Hospital Organization - Osaka National Hospital (ONH)
Osaka, Osaka-shi, Osaka-fu, 540-0006
Kindai University Hospital
Osaka, Osakasayama Shi, 589-8511
The Cancer Institute Hospital Of JFCR
Tokyo, 135-8550
Poland4 sites
Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu
Ostrów Wielkopolski, Poznan, 60-569
Szpital Kliniczny Przemienienia Pańskiego.University Hospital, Chemotherapy Department
Poznan
M Sklodowska Curie Memorial Cancer Center
Warsaw, 02-034
M Sklodowska Curie Memorial Cancer Center
Warsaw
United Kingdom4 sites
Royal Marsden Hospital NHS
London, SW3 6JJ
Sarah Cannon Research Institute UK
London, W1G 6AD
Royal Marsden Hospital NHS
London
Sarah Cannon
London
France3 sites
Centre Georges-Franois Leclerc
Dijon, 21000
CHU Nantes
Nantes, 44000
Hospital St Antoine
Paris, 75012
About this study
Official title: A Multi-Center, Open-Label, Phase 2 Study to Evaluate Safety and Efficacy of U3-1402 in Subjects With Advanced or Metastatic Colorectal Cancer (CRC)
This study is designed to primarily evaluate the safety and efficacy of U3-1402 in participants with advanced or metastatic colorectal cancer (CRC) who have received at least 2 prior lines of therapy and will explore clinical benefit according to human epidermal growth factor receptor 3 (HER3) tumor expression level in otherwise refractory tumors.
Read the detailed description
There will be 2 cohorts with enrollment in 2 parts. Participants will be treated on Day 1 of each 21-day cycle (every 3 weeks) with U3-1402 5.6 mg/kg intravenous (IV). The estimated treatment period is approximately 8 months and the follow-up period is approximately 4 months.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Patritumab Deruxtecan
- Keywords
- Metastatic Colorectal Cancer, U3-1402
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Patritumab DeruxtecanDrug
Also called U3-1402
U3-1402 will be dosed at 5.6 mg/kg as an intravenous (IV) infusion administered on Day 1 of each 21-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: HER3 High (IHC 3+, 2+) | Experimental | Cohort 1 participants will have high tumor expression levels of human epidermal receptor 3 (HER3) in a pre-treatment biopsy specimen. Receives: Drug: Patritumab Deruxtecan |
| Cohort 2: HER3 Low/Negative (IHC 1+, 0) | Experimental | Cohort 2 participants will have low or negative tumor expression levels of human epidermal receptor 3 (HER3) expression levels in a pre-treatment biopsy specimen. Receives: Drug: Patritumab Deruxtecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR) As Assessed By Blinded Independent Central Review (BICR) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
ORR defined as the proportion of participants with a best overall response of confirmed complete response (CR) or partial response (PR) as assessed by blinded independent central review. CR was defined as a disappearance of all lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesion based on RECIST v1.1.
Measured: From Baseline (Day 0) to data cut off (up to approximately 16.5 months)
Secondary outcomes (16)
Duration of Response (DoR) As Assessed by Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
DoR defined as the time from the first documented response (CR or PR) to the date of disease progression or death due to any cause. CR was defined as a disappearance of all lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions based on RECIST v1.1.
Measured: From Baseline (Day 0) to data cut off (up to approximately 16.5 months)
Objective Response Rate (ORR) As Assessed by Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
ORR defined as the proportion of participants with a best overall response (BOR) of confirmed complete response (CR) or partial response (PR) as assessed by Investigator. CR was defined as a disappearance of all lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesion based on RECIST v1.1.
Measured: From Baseline (Day 0) to data cut off (up to approximately 16.5 months)
Disease Control Rate (DCR) by Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
DCR is defined as the proportion of participants who achieved a confirmed best overall response (BOR) of complete response (CR), partial response (PR), or stable disease (SD) as assessed by blinded independent central review or by the Investigator. Based on RECIST v1.1, CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions.
Measured: From Baseline (Day 0) to data cut off (up to approximately 16.5 months)
Time to Tumor Response (TTR) As Assessed by Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
TTR defined as the time from the start of study treatment to the date of the first documentation of objective response (complete response [CR] or partial response [PR]) that is subsequently confirmed by Blinded Independent Central Review or by the Investigator. CR was defined as a disappearance of all lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions based on RECIST v1.1.
Measured: From Baseline (Day 0) to data cut off (up to approximately 16.5 months)
Progression-free Survival (PFS) Assessed by Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
PFS is defined as the time from the start of study treatment to the date of the first documentation of objective PD or death due to any cause, whichever is earlier.
Measured: From Baseline (Day 0) to data cut off (up to approximately 16.5 months)
Overall Survival (OS) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
OS defined as the time from the start of study treatment to the date of death due to any cause.
Measured: From Baseline (Day 0) to data cut off (up to approximately 16.5 months)
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Other Safety Parameters During the Study
TEAEs, study-drug related TEAE, serious adverse events (SAE), study-drug related SAE, and adverse events of special interest (eg. interstitial lung disease and elevation of aminotransferases and total bilirubin) were assessed. A TEAE was defined as an AE with a start or worsening date during the on-treatment period. An SAE was an AE that resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event.
Measured: From Baseline (Day 0) to data cut off (up to approximately 16.5 months)
Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline)
Blood samples were collected to assess the immunogenicity of U3-1402.
Measured: At Baseline, and post-Baseline. Post-Baseline including any of the following timepoints- Cycle 1, Days 1&8; Cycles 2&4 and every 2 cycles thereafter, Day 1 (each cycle, 21 days), and at EOT (~16.5 months).
Number of Participants Who Have Treatment-emergent Anti-Drug Antibody (ADA)
Blood samples were collected to assess the immunogenicity of U3-1402. Treatment-emergent ADA was defined as participants with a negative ADA status at Baseline who had a positive ADA status post-Baseline (treatment-induced ADA), or participants with a positive ADA status at both Baseline and post-Baseline but with an increase of at least 4-fold in ADA titer from Baseline to post-Baseline (treatment-boosted ADA), or participants who had missing ADA data at Baseline and had a positive ADA status post-Baseline.
Measured: At Baseline, and post-Baseline. Post-Baseline including any of the following timepoints- Cycle 1, Days 1&8; Cycles 2&4 and every 2 cycles thereafter, Day 1 (each cycle, 21 days), and at EOT (~16.5 months).
Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
Serum PK parameter Cmax (antibody drug conjugate [ADC], total anti-HER3 antibody, and MAAA-1181a) were assessed in the full PK sampling cohort using noncompartmental methods.
Measured: At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 and Cycle 3 (each cycle is 21 days)
Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) of MAAA-1181a Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
Serum PK parameter Cmax of MAAA-1181a was assessed in the full PK sampling cohort using noncompartmental methods.
Measured: At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 and Cycle 3 (each cycle is 21 days)
Pharmacokinetic Parameter Time to Reach Maximum Serum Concentration (Tmax) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
Serum PK parameter Tmax (antibody drug conjugate [ADC], total anti-HER3 antibody, and MAAA-1181a) were assessed in the full PK sampling cohort using noncompartmental methods.
Measured: At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 and Cycle 3 (each cycle is 21 days)
Pharmacokinetic ParameterTrough Serum Concentration (Ctrough) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
Serum PK parameter Ctrough (antibody drug conjugate [ADC] and total anti-HER3 antibody) were assessed in the full PK sampling cohort using noncompartmental methods.
Measured: At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 and Cycle 3 (each cycle is 21 days)
Pharmacokinetic ParameterTrough Serum Concentration (Ctrough) of MAAA-1181a Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
Serum PK parameter Ctrough of MAAA-1181a was assessed in the full PK sampling cohort using noncompartmental methods.
Measured: At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 and Cycle 3 (each cycle is 21 days)
Pharmacokinetic of Area Under the Serum Concentration-Time Curve Up to Last Quantifiable Time (AUClast) and During Dosing Interval (AUCtau) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
Serum PK parameter AUC (antibody drug conjugate [ADC], total anti-HER3 antibody, and MAAA-1181a) were assessed in the full PK sampling cohort using noncompartmental methods.
Measured: At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 and Cycle 3 (each cycle is 21 days)
Pharmacokinetic of Area Under the Serum Concentration-Time Curve Up to Last Quantifiable Time (AUClast) and During Dosing Interval (AUCtau) of MAAA-1181a Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
Serum PK parameter AUC of MAAA-1181a was assessed in the full PK sampling cohort using noncompartmental methods.
Measured: At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 and Cycle 3 (each cycle is 21 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2020
- Study start14 Sep 2020
- Primary completion3 Feb 2022
- Study completion3 Feb 2022
Why it stopped: Study was terminated early given the Interim Analysis for Part 1 (signal finding) did not meet pre-specified criteria and will not proceed to Part 2. Sponsor will proceed closing the study.
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 Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Daiichi SankyoThe 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Daiichi Sankyo
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Global Clinical Leader, Study director, Daiichi Sankyo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04479436
- Sponsor's protocol ID
- U31402-A-U202
- Other IDs
- 2019-004418-32, 2019
- Status last verified
- May 2025
- First submitted
- 13 Jul 2020
- Last updated
- 18 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Center, Open-Label, Phase 2 Study to Evaluate Safety and Efficacy of U3-1402 in Subjects With Advanced or Metastatic Colorectal Cancer (CRC)
- ClinicalTrials.gov ID
- NCT04479436
- Acronym / sponsor ID
- U31402-A-U202
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- Metastatic Colorectal Cancer, U3-1402
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated early given the Interim Analysis for Part 1 (signal finding) did not meet pre-specified criteria and will not proceed to Part 2. Sponsor will proceed closing the study.
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Daiichi SankyoIndustry (pharma, biotech, devices)
- Study start
- 14 Sep 2020 (actual)
- Primary completion
- 3 Feb 2022 (actual)
- Study completion
- 3 Feb 2022 (actual)
- First posted
- 21 Jul 2020 (actual)
- Results
- Posted 18 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to primarily evaluate the safety and efficacy of U3-1402 in participants with advanced or metastatic colorectal cancer (CRC) who have received at least 2 prior lines of therapy and will explore clinical benefit according to human epidermal growth factor receptor 3 (HER3) tumor expression level in otherwise refractory tumors.
Detailed description
There will be 2 cohorts with enrollment in 2 parts. Participants will be treated on Day 1 of each 21-day cycle (every 3 weeks) with U3-1402 5.6 mg/kg intravenous (IV). The estimated treatment period is approximately 8 months and the follow-up period is approximately 4 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: HER3 High (IHC 3+, 2+) | Experimental | Drug: Patritumab DeruxtecanCohort 1 participants will have high tumor expression levels of human epidermal receptor 3 (HER3) in a pre-treatment biopsy specimen. |
| Cohort 2: HER3 Low/Negative (IHC 1+, 0) | Experimental | Drug: Patritumab DeruxtecanCohort 2 participants will have low or negative tumor expression levels of human epidermal receptor 3 (HER3) expression levels in a pre-treatment biopsy specimen. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- Participant has provided written informed consent prior to the start of any study specific procedures.
- Participants ≥18 years (follow local regulatory requirements if the legal age of consent for study participation is >18 years old).
- Pathological/histological confirmation of advanced or metastatic colon or rectal adenocarcinoma.
- Must be resistant, refractory, or intolerant to at least 2 prior lines of systemic therapy, that must include all of the following agents:
- Has at least 1 measurable lesion confirmed by blinded independent central review (BICR) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1.
Key exclusion criteria (28 listed)
- Any history of interstitial lung disease (including pulmonary fibrosis or radiation pneumonitis), has current interstitial lung disease (ILD), or is suspected to have such disease by imaging during screening.
- Clinically severe pulmonary compromise (based on Investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to:
- Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to Cycle 1 Day 1. Participants who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the study.
- Evidence of leptomeningeal disease.
- Evidence of clinically active spinal cord compression or brain metastases
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 |
|---|---|---|
| Patritumab DeruxtecanAlso: U3-1402U3-1402 will be dosed at 5.6 mg/kg as an intravenous (IV) infusion administered on Day 1 of each 21-day cycle. | Drug | Cohort 1: HER3 High (IHC 3+, 2+), Cohort 2: HER3 Low/Negative (IHC 1+, 0) |
Primary outcome
Objective Response Rate (ORR) As Assessed By Blinded Independent Central Review (BICR) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
Time frame: From Baseline (Day 0) to data cut off (up to approximately 16.5 months)
ORR defined as the proportion of participants with a best overall response of confirmed complete response (CR) or partial response (PR) as assessed by blinded independent central review. CR was defined as a disappearance of all lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesion based on RECIST v1.1.
16 secondary outcomes
Duration of Response (DoR) As Assessed by Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
Time frame: From Baseline (Day 0) to data cut off (up to approximately 16.5 months)
Objective Response Rate (ORR) As Assessed by Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
Time frame: From Baseline (Day 0) to data cut off (up to approximately 16.5 months)
Disease Control Rate (DCR) by Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
Time frame: From Baseline (Day 0) to data cut off (up to approximately 16.5 months)
Time to Tumor Response (TTR) As Assessed by Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
Time frame: From Baseline (Day 0) to data cut off (up to approximately 16.5 months)
Progression-free Survival (PFS) Assessed by Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
Time frame: From Baseline (Day 0) to data cut off (up to approximately 16.5 months)
Overall Survival (OS) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
Time frame: From Baseline (Day 0) to data cut off (up to approximately 16.5 months)
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Other Safety Parameters During the Study
Time frame: From Baseline (Day 0) to data cut off (up to approximately 16.5 months)
Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline)
Time frame: At Baseline, and post-Baseline. Post-Baseline including any of the following timepoints- Cycle 1, Days 1&8; Cycles 2&4 and every 2 cycles thereafter, Day 1 (each cycle, 21 days), and at EOT (~16.5 months).
Number of Participants Who Have Treatment-emergent Anti-Drug Antibody (ADA)
Time frame: At Baseline, and post-Baseline. Post-Baseline including any of the following timepoints- Cycle 1, Days 1&8; Cycles 2&4 and every 2 cycles thereafter, Day 1 (each cycle, 21 days), and at EOT (~16.5 months).
Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
Time frame: At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 and Cycle 3 (each cycle is 21 days)
Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) of MAAA-1181a Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
Time frame: At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 and Cycle 3 (each cycle is 21 days)
Pharmacokinetic Parameter Time to Reach Maximum Serum Concentration (Tmax) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
Time frame: At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 and Cycle 3 (each cycle is 21 days)
Pharmacokinetic ParameterTrough Serum Concentration (Ctrough) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
Time frame: At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 and Cycle 3 (each cycle is 21 days)
Pharmacokinetic ParameterTrough Serum Concentration (Ctrough) of MAAA-1181a Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
Time frame: At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 and Cycle 3 (each cycle is 21 days)
Pharmacokinetic of Area Under the Serum Concentration-Time Curve Up to Last Quantifiable Time (AUClast) and During Dosing Interval (AUCtau) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
Time frame: At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 and Cycle 3 (each cycle is 21 days)
Pharmacokinetic of Area Under the Serum Concentration-Time Curve Up to Last Quantifiable Time (AUClast) and During Dosing Interval (AUCtau) of MAAA-1181a Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer
Time frame: At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 and Cycle 3 (each cycle is 21 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
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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.
Global Clinical Leader study director
Daiichi Sankyo
46 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Patritumab Deruxtecan in people with Metastatic Colorectal Cancer, run by Daiichi Sankyo at 46 sites in 8 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 27 inclusion and 28 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: stopped early, as of the sponsor's last update on 18 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 46 sites in United States, Spain, Japan, Poland, United Kingdom and 3 more countries. 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 18 May 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?
Objective Response Rate (ORR) As Assessed By Blinded Independent Central Review (BICR) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer (time frame: From Baseline (Day 0) to data cut off (up to approximately 16.5 months)). 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 18 May 2025.