Gastrointestinal Neoplasms; Esophageal, Stomach, Pancreas, Colon Neoplasms; Malignant Tumors of Digestive Organ; Advanced Gastrointestinal MalignanciesPhase 1NCT03449030

A Study of TAK-164 in Participants With Advanced Gastrointestinal (GI) Cancer Expressing Guanylyl Cyclase C (GCC)

A Phase 1 study testing TAK-164 and 89Zr-TAK-164 in people with Gastrointestinal Neoplasms; Esophageal, Stomach, Pancreas, Colon Neoplasms; Malignant Tumors of Digestive Organ; Advanced Gastrointestinal Malignancies, run by Millennium Pharmaceuticals, Inc. at 4 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

The purpose of this study is to evaluate the safety of TAK-164 and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) and schedule. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Gastrointestinal Neoplasms; Esophageal, Stomach, Pancreas, Colon Neoplasms; Malignant Tumors of Digestive Organ; Advanced Gastrointestinal Malignancies
What is being tested?: TAK-164 and 89Zr-TAK-164
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 31 participants
Where: 4 sitesUnited States
Study dates: 23 Apr 2018to 27 Feb 2020
Phase: Phase 1
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

Histologically or cytologically confirmed measurable advanced and/or metastatic solid GI tumor that expresses GCC protein (H-score greater than or equal to [>=] 10), for which standard treatment is no longer effective or does not offer curative or life-prolonging benefit. For the escalation part of the study (Part A), GI malignancies include, but are not limited to, metastatic colorectal carcinoma (mCRC), gastric carcinoma, esophageal carcinoma, small intestine cancer, and pancreatic cancer. The expansion part of the study (Part B) is limited to participants with CRC expressing a high-level of GCC (H-Score >=150) and gastric carcinoma (H-Score >=10). Part C includes participants with CRC and gastric carcinoma (H-score >=10 for both indications).
o Part B of the study will be limited to participants with 2 or 3 prior lines of systemic standard of care therapy.
Male or female participants 18 years or older.
Adequate bone marrow function, defined as an absolute neutrophil count (ANC) of >=1.5*10^9 per liter (/L), platelet count >=100*10^9/L, and hemoglobin >=9 gram per deciliter (g/dL). Receiving transfusions or hematopoietic growth factors to meet enrollment criteria is not allowed within 14 days preceding the first dose of study drug.
Adequate hepatic function with total bilirubin less than or equal to (<=) 1.5* upper limit of normal (ULN), serum ALT and AST must be less than (<) 2.5*ULN (AST and ALT may be elevated up to 3*ULN if the elevation can be reasonably ascribed to the presence of metastatic disease in liver), serum albumin > 3.0 g/dL.
Adequate renal function as defined by creatinine CL >= 60 milliliter per minute (mL/min).

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Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1.
Life expectancy of at least 12 weeks.
Completion of prior chemotherapy, biologic therapy, immunotherapy, or radiation therapy at least 4 weeks prior to enrollment.
Resolution of all toxic effects of prior treatments (except alopecia) to Grade <=1 NCI CTCAE, version 5.
A portion of participants should have tumors amenable for serial biopsy and a willingness to provide consent for pharmacodynamic assessment.
Additionally for Part C (imaging sub study), participant must fulfill the following criteria:
At least 1 extrahepatic metastatic lesion >=2 centimeter (cm) in the longest diameter.

Who cannot join

Treatment with anticancer chemotherapy or biologic therapy or with an experimental anticancer agent within 28 days of the initial dose of study drug.
Diagnosed or treated for another malignancy within 2 years before administration of the first dose of study drug, or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
Participant has a history of severe allergic or anaphylactic reactions to recombinant proteins or excipients used in TAK-164 formulation or 89Zr-TAK-164 formulation.
Use of strong cytochrome P3A (CYP3A) inhibitors and CYP3A inducers or inhibitors or modulators of P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) within 1 week before the first dose of study drug.
For participants enrolled in studies in which tumor biopsies are obtained:
Known bleeding diathesis or history of abnormal bleeding, or any other known coagulation abnormalities that would contraindicate the tumor biopsy procedure.
Ongoing therapy with any anticoagulant or antiplatelet agents (example, aspirin, clopidogrel, heparin, or warfarin).
Participant has concurrent alcohol abuse or a history of drug-induced liver injury (DILI).

Trial locations and contacts

4 sites in 1 country.

United States4 sites

University of Colorado Cancer Center
Aurora, Colorado, 80045
Massachusetts General Hospital
Boston, Massachusetts, 02114-2621
SCRI - Tennessee Oncology Nashville - Southern Hills Clinic
Nashville, Tennessee, 37205
Moffitt Cancer Center
Tampa, Florida, 33612

Other trials in United States

About this study

Official title: An Open-Label, Dose Escalation, Phase 1, First-in-Human Study of TAK-164, an Antibody-Drug Conjugate, in Patients With Advanced Gastrointestinal Cancers Expressing Guanylyl Cyclase C

The purpose of this study is to evaluate the safety of TAK-164 and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) and schedule.

Read the detailed description

The drug being tested in this study is a novel antibody-drug conjugate (ADC) called TAK-164. TAK-164 is being evaluated in participants with advanced GCC-positive GI cancer (Part A) or colorectal carcinoma (CRC) and gastric carcinoma (Part B and Part C) to determine safety, tolerability, and pharmacokinetics (PK) and MTD/RP2D of TAK-164, as well as the preliminary efficacy. The study will include approximately 100 evaluable participants.

In Part A (Escalation), approximately 25 participants with GI carcinoma will be enrolled. Those include participants with various GI malignancies such as carcinomas of esophagus, stomach, colon, and pancreas. The starting dose for Arm 1 will be 0.004 mg/kg of TAK-164 administered intravenously on Day 1 Q3W and the maximal dose will not exceed 0.19 mg/kg Q3W.

In Part B (Expansion), approximately 50 participants will be enrolled to receive TAK-164 infusion at determined RP2D in Part A. Participants will follow the Q3W schedule and will be followed until PD, unacceptable toxicity, or until they choose to withdraw consent.

In Part C (Imaging substudy to be conducted in the Netherlands only), approximately 25 participants with GCC-expressing metastatic colorectal carcinoma (mCRC) will be enrolled to receive 89Zr-TAK-164 and unlabeled TAK-164 at determined RP2D in Part A.

This multi-center trial will be conducted in the United States and the Netherlands. The overall time to participate in this study is up to 55 months. Participants will attend an end of study (EOS) visit 30 days after the last dose of TAK-164 or just prior to the start of subsequent antineoplastic therapy, whichever occurs first.

Conditions: Gastrointestinal Neoplasms; Esophageal, Stomach, Pancreas, Colon Neoplasms; Malignant Tumors of Digestive Organ; Advanced Gastrointestinal Malignancies
Being tested: TAK-164, 89Zr-TAK-164
Keywords: Drug Therapy
Medical subject headings: Gastrointestinal Neoplasms, Colonic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TAK-164Drug
TAK-164 intravenous infusion.
89Zr-TAK-164Drug
89Zr-TAK-164 intravenous infusion

Study groups in NCT03449030
Study group	Role	What they receive
Part A Escalation Stage: TAK-164 Q3W	Experimental	TAK-164 0.004 milligram per kilogram (mg/kg) starting dose, intravenous infusion, until PD, unacceptable toxicity or discontinuation by participant. Dose escalation will be performed to determine the MTD and/or RP2D. Receives: Drug: TAK-164
Part B Expansion Stage: TAK-164 Q3W	Experimental	TAK-164, intravenous infusion, until PD, unacceptable toxicity or discontinuation by participant. TAK-164 RP2D dose to be decided based on safety, PK, pharmacodynamics and antitumor response data observed in Part A escalation stage. Receives: Drug: TAK-164
Part C Imaging Substudy: 89Zr-TAK-164 and TAK-164	Experimental	89Zr-TAK-164, intravenous infusion, followed by unlabeled TAK-164, intravenous infusion in combination with 89Zr-TAK-164, intravenous infusion, and further followed by unlabeled TAK-164, intravenous infusion, until PD, unacceptable toxicity or discontinuation by participant. TAK-164 recommended imaging dose (RID) or RP2D dose to be decided based on safety, PK, PD and antitumor response data observed in Part A escalation stage. Receives: Drug: TAK-164; Drug: 89Zr-TAK-164

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Dose-limiting Toxicities (DLTs)
DLTs were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5. DLT was defined as any of the following adverse events (AEs) that occurred and were considered by the investigator to be related to therapy with study drug: hematologic toxicities were, Grade 4 neutropenia (absolute neutrophil count [ANC] less than (<) 500 cells/cubic millimeter [mm^3]), thrombocytopenia (platelets <25,000/mm^3), febrile neutropenia (ANC <1000/mm^3) with fever (greater than [>] 38.3 degree Celsius or sustained temperature of greater than or equal to (>=) 38 degree Celsius, Grade 3 or greater thrombocytopenia with clinically meaningful bleeding at any time, Grade 3 or greater nausea and/or emesis that occurs despite the use of optimal anti-emetic prophylaxis and Grade 3 or greater diarrhea that occurs despite optimal supportive care measures and any other Grade 3 or greater nonhematologic toxicity except brief (<1 week) Grade 3 fatigue.
Measured: Baseline up to Month 22
Percentage of Participants With Adverse Events (AEs)
Measured: From first dose of study drug up to 30 days following the last dose of study drug (up to 22 months)
Percentage of Participants With Grade 3 or Above AEs
AE Grades were evaluated as per NCI CTCAE, version 5. Graded from Grade 1: Mild asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated, Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL), Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL, Grade 4: Life-threatening consequences; urgent intervention indicated, Grade 5: Death related AE. Higher grade indicates more severe condition.
Measured: From first dose of study drug up to 30 days following the last dose of study drug (up to 22 months)
Percentage of Participants With Drug-related AEs
Measured: From first dose of study drug up to 30 days following the last dose of study drug (up to 22 months)
Percentage of Participants With Drug-related Grade 3 or Above AEs
AE Grades were evaluated as per NCI CTCAE, version 5. Graded from Grade 1: mild asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated, Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL, Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL, Grade 4: Life-threatening consequences; urgent intervention indicated, Grade 5: death related AE. Higher grade indicates more severe condition.
Measured: From first dose of study drug up to 30 days following the last dose of study drug (up to 22 months)
Percentage of Participants With Serious Adverse Events (SAEs)
Measured: From first dose of study drug up to 30 days following the last dose of study drug (up to 22 months)
Percentage of Participants With AEs Leading to Discontinuation
Measured: From first dose of study drug up to 30 days following the last dose of study drug (up to 22 months)
Recommended Phase 2 Dose (RP2D) of TAK-164
RP2D was the highest safe dose that could be applied to the expansion phase.
Measured: Baseline up to Month 22

Secondary outcomes (9)

Cmax: Maximum Observed Plasma Concentration for TAK-164
Measured: Cycles 1 and 2 Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose (Cycle length = 21 days)
Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-164
Measured: Cycles 1 and 2 Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose (Cycle length = 21 days)
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration for TAK-164
Measured: Cycles 1 and 2 Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose (Cycle length = 21 days)
Ctrough: Observed Concentration Measured at the End of a Dosing Interval for TAK-164
Measured: Cycles 1 and 2 Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose (Cycle length = 21 days)
Overall Response Rate (ORR)
ORR was assessed by the investigator based on modified Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. ORR was defined as the percentage of participants who had complete response (CR) or partial response (PR). CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to <10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum longest diameter.
Measured: From start of study treatment until the start of subsequent anti cancer therapy ( up to Month 22)
Disease Control Rate (DCR)
DCR was defined as the percentage of participants with CR, PR or stable disease (SD). DCR was assessed based on modified RECIST version 1.1 criteria. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest diameter since the treatment started.
Measured: Baseline up to Month 22
Duration of Response (DOR)
DOR was defined as the time from the date of first documentation of a response (CR or PR) to the date of first documented PD or death due to any cause, whichever occurred first based on modified RECIST version 1.1 criteria. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum longest diameters. PD was >=20% increase in sum of diameters of target lesions, reference-smallest sum recorded in study (sum at baseline if that was smallest). Sum of diameters must have absolute increase of >=5 mm. Appearance of >=1 new lesions also considered PD.
Measured: From the date of first documentation of a response (CR or PR) to the date of first documented PD or death due to any cause, whichever occurred first (up to 22 months)
Progression-free Survival (PFS)
PFS was defined as the time from date of first study drug administration to the day of first documented PD or death due to any cause, whichever occurred first according to modified RECIST version 1.1 criteria. PD was >= 20% increase in sum of diameters of target lesions, reference-smallest sum recorded in study (sum at baseline if that was smallest). Sum of diameters must have absolute increase of >=5 mm. Appearance of >=1 new lesions also considered PD. PFS was censored at the last response assessment that is stable disease or better, prior to receipt of subsequent anticancer therapy, if applicable. Participants with no post-baseline assessments was censored at Day 1.
Measured: From date of first study drug administration to the day of first documented PD or death due to any cause, whichever occurred first (up to 22 months)
Number of Participants With Positive Antidrug Antibody (ADA) Levels in Serum
Measured: Baseline up to Month 22

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 Apr 201827 Feb 2020

First posted28 Feb 2018
Study start23 Apr 2018
Primary completion27 Feb 2020
Study completion27 Feb 2020

Why it stopped: Insufficient clinical benefit to participants at the selected recommended phase 2 (RP2D) dose in Part A.

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.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Gastrointestinal Neoplasms; Esophageal, Stomach, Pancreas, Colon Neoplasms; Malignant Tumors of Digestive Organ; Advanced Gastrointestinal MalignanciesStudies of the same condition, open and under way.
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 1
Primary purpose: Other
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 31 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03449030
Sponsor's protocol ID: TAK-164-1001
Other IDs: U1111-1207-9923, 2018-002214-12, 2018
Status last verified: Feb 2021
First submitted: 22 Feb 2018
Last updated: 22 Mar 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Publications

Kim R, Leal AD, Parikh A, Ryan DP, Wang S, Bahamon B, Gupta N, Moss A, Pye J, Miao H, Inguilizian H, Cleary JM. A phase I, first-in-human study of TAK-164, an antibody-drug conjugate, in patients with advanced gastrointestinal cancers expressing guanylyl cyclase C. Cancer Chemother Pharmacol. 2023 Apr;91(4):291-300. doi: 10.1007/s00280-023-04507-w. Epub 2023 Feb 4.
PubMed 36738333
Abu-Yousif AO, Cvet D, Gallery M, Bannerman BM, Ganno ML, Smith MD, Lai KC, Keating TA, Stringer B, Kamali A, Eng K, Koseoglu S, Zhu A, Xia CQ, Landen MS, Borland M, Robertson R, Bolleddula J, Qian MG, Fretland J, Veiby OP. Preclinical Antitumor Activity and Biodistribution of a Novel Anti-GCC Antibody-Drug Conjugate in Patient-derived Xenografts. Mol Cancer Ther. 2020 Oct;19(10):2079-2088. doi: 10.1158/1535-7163.MCT-19-1102. Epub 2020 Aug 11.
PubMed 32788205

Study at a glance

From the registry record, last updated by the sponsor on 22 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-Label, Dose Escalation, Phase 1, First-in-Human Study of TAK-164, an Antibody-Drug Conjugate, in Patients With Advanced Gastrointestinal Cancers Expressing Guanylyl Cyclase C
ClinicalTrials.gov ID: NCT03449030
Acronym / sponsor ID: TAK-164-1001
Conditions: Gastrointestinal Neoplasms; Esophageal, Stomach, Pancreas, Colon Neoplasms; Malignant Tumors of Digestive Organ; Advanced Gastrointestinal Malignancies
Keywords: Drug Therapy
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: Insufficient clinical benefit to participants at the selected recommended phase 2 (RP2D) dose in Part A.
Enrolment: 31 participants (actual)
Lead sponsor: Millennium Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
Study start: 23 Apr 2018 (actual)
Primary completion: 27 Feb 2020 (actual)
Study completion: 27 Feb 2020 (actual)
First posted: 28 Feb 2018 (actual)
Results: Posted 22 Mar 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of this study is to evaluate the safety of TAK-164 and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) and schedule.

Detailed description

Study design

Primary purpose: Other
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Part A Escalation Stage: TAK-164 Q3W	Experimental	Drug: TAK-164TAK-164 0.004 milligram per kilogram (mg/kg) starting dose, intravenous infusion, until PD, unacceptable toxicity or discontinuation by participant. Dose escalation will be performed to determine the MTD and/or RP2D.
Part B Expansion Stage: TAK-164 Q3W	Experimental	Drug: TAK-164TAK-164, intravenous infusion, until PD, unacceptable toxicity or discontinuation by participant. TAK-164 RP2D dose to be decided based on safety, PK, pharmacodynamics and antitumor response data observed in Part A escalation stage.
Part C Imaging Substudy: 89Zr-TAK-164 and TAK-164	Experimental	Drug: TAK-164, Drug: 89Zr-TAK-16489Zr-TAK-164, intravenous infusion, followed by unlabeled TAK-164, intravenous infusion in combination with 89Zr-TAK-164, intravenous infusion, and further followed by unlabeled TAK-164, intravenous infusion, until PD, unacceptable toxicity or discontinuation by participant. TAK-164 recommended imaging dose (RID) or RP2D dose to be decided based on safety, PK, PD and antitumor response data observed in Part A escalation stage.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (13 listed)

Histologically or cytologically confirmed measurable advanced and/or metastatic solid GI tumor that expresses GCC protein (H-score greater than or equal to [>=] 10), for which standard treatment is no longer effective or does not offer curative or life-prolonging benefit. For the escalation part of the study (Part A), GI malignancies include, but are not limited to, metastatic colorectal carcinoma (mCRC), gastric carcinoma, esophageal carcinoma, small intestine cancer, and pancreatic cancer. The expansion part of the study (Part B) is limited to participants with CRC expressing a high-level of GCC (H-Score >=150) and gastric carcinoma (H-Score >=10). Part C includes participants with CRC and gastric carcinoma (H-score >=10 for both indications).
o Part B of the study will be limited to participants with 2 or 3 prior lines of systemic standard of care therapy.
Male or female participants 18 years or older.
Adequate bone marrow function, defined as an absolute neutrophil count (ANC) of >=1.5*10^9 per liter (/L), platelet count >=100*10^9/L, and hemoglobin >=9 gram per deciliter (g/dL). Receiving transfusions or hematopoietic growth factors to meet enrollment criteria is not allowed within 14 days preceding the first dose of study drug.
Adequate hepatic function with total bilirubin less than or equal to (<=) 1.5* upper limit of normal (ULN), serum ALT and AST must be less than (<) 2.5*ULN (AST and ALT may be elevated up to 3*ULN if the elevation can be reasonably ascribed to the presence of metastatic disease in liver), serum albumin > 3.0 g/dL.

Key exclusion criteria (8 listed)

Treatment with anticancer chemotherapy or biologic therapy or with an experimental anticancer agent within 28 days of the initial dose of study drug.
Diagnosed or treated for another malignancy within 2 years before administration of the first dose of study drug, or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
Participant has a history of severe allergic or anaphylactic reactions to recombinant proteins or excipients used in TAK-164 formulation or 89Zr-TAK-164 formulation.
Use of strong cytochrome P3A (CYP3A) inhibitors and CYP3A inducers or inhibitors or modulators of P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) within 1 week before the first dose of study drug.
For participants enrolled in studies in which tumor biopsies are obtained:

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
TAK-164TAK-164 intravenous infusion.	Drug	Part A Escalation Stage: TAK-164 Q3W, Part B Expansion Stage: TAK-164 Q3W, Part C Imaging Substudy: 89Zr-TAK-164 and TAK-164
89Zr-TAK-16489Zr-TAK-164 intravenous infusion	Drug	Part C Imaging Substudy: 89Zr-TAK-164 and TAK-164

Primary outcome

Number of Participants With Dose-limiting Toxicities (DLTs)
Time frame: Baseline up to Month 22
DLTs were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5. DLT was defined as any of the following adverse events (AEs) that occurred and were considered by the investigator to be related to therapy with study drug: hematologic toxicities were, Grade 4 neutropenia (absolute neutrophil count [ANC] less than (<) 500 cells/cubic millimeter [mm^3]), thrombocytopenia (platelets <25,000/mm^3), febrile neutropenia (ANC <1000/mm^3) with fever (greater than [>] 38.3 degree Celsius or sustained temperature of greater than or equal to (>=) 38 degree Celsius, Grade 3 or greater thrombocytopenia with clinically meaningful bleeding at any time, Grade 3 or greater nausea and/or emesis that occurs despite the use of optimal anti-emetic prophylaxis and Grade 3 or greater diarrhea that occurs despite optimal supportive care measures and any other Grade 3 or greater nonhematologic toxicity except brief (<1 week) Grade 3 fatigue.
Percentage of Participants With Adverse Events (AEs)
Time frame: From first dose of study drug up to 30 days following the last dose of study drug (up to 22 months)
Percentage of Participants With Grade 3 or Above AEs
Time frame: From first dose of study drug up to 30 days following the last dose of study drug (up to 22 months)
AE Grades were evaluated as per NCI CTCAE, version 5. Graded from Grade 1: Mild asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated, Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL), Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL, Grade 4: Life-threatening consequences; urgent intervention indicated, Grade 5: Death related AE. Higher grade indicates more severe condition.
Percentage of Participants With Drug-related AEs
Time frame: From first dose of study drug up to 30 days following the last dose of study drug (up to 22 months)
Percentage of Participants With Drug-related Grade 3 or Above AEs
Time frame: From first dose of study drug up to 30 days following the last dose of study drug (up to 22 months)
AE Grades were evaluated as per NCI CTCAE, version 5. Graded from Grade 1: mild asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated, Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL, Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL, Grade 4: Life-threatening consequences; urgent intervention indicated, Grade 5: death related AE. Higher grade indicates more severe condition.
Percentage of Participants With Serious Adverse Events (SAEs)
Time frame: From first dose of study drug up to 30 days following the last dose of study drug (up to 22 months)
Percentage of Participants With AEs Leading to Discontinuation
Time frame: From first dose of study drug up to 30 days following the last dose of study drug (up to 22 months)
Recommended Phase 2 Dose (RP2D) of TAK-164
Time frame: Baseline up to Month 22
RP2D was the highest safe dose that could be applied to the expansion phase.

9 secondary outcomes

Cmax: Maximum Observed Plasma Concentration for TAK-164
Time frame: Cycles 1 and 2 Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose (Cycle length = 21 days)
Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-164
Time frame: Cycles 1 and 2 Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose (Cycle length = 21 days)
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration for TAK-164
Time frame: Cycles 1 and 2 Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose (Cycle length = 21 days)
Ctrough: Observed Concentration Measured at the End of a Dosing Interval for TAK-164
Time frame: Cycles 1 and 2 Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose (Cycle length = 21 days)
Overall Response Rate (ORR)
Time frame: From start of study treatment until the start of subsequent anti cancer therapy ( up to Month 22)
Disease Control Rate (DCR)
Time frame: Baseline up to Month 22
Duration of Response (DOR)
Time frame: From the date of first documentation of a response (CR or PR) to the date of first documented PD or death due to any cause, whichever occurred first (up to 22 months)
Progression-free Survival (PFS)
Time frame: From date of first study drug administration to the day of first documented PD or death due to any cause, whichever occurred first (up to 22 months)
Number of Participants With Positive Antidrug Antibody (ADA) Levels in Serum
Time frame: Baseline up to Month 22

Results and safety

Results posted to the registry on 22 Mar 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part A: TAK-164 0.004 mg/kg	1	0
Part A: TAK-164 0.008 mg/kg	1	0
Part A: TAK-164 0.016 mg/kg	1	0
Part A: TAK-164 0.032 mg/kg	5	0
Part A: TAK-164 0.064 mg/kg	7	0
Part A: TAK-164 0.12 mg/kg	7	0
Part A: TAK-164 0.16 mg/kg	2	0
Part A: TAK-164 0.19 mg/kg	3	0
Part A: TAK-164 0.25 mg/kg	3	0
Part A: TAK-164 0.32 mg/kg	1	0

Primary outcome: Number of Participants With Dose-limiting Toxicities (DLTs)

Time frame: Baseline up to Month 22. Count of participants. Unit: Participants

Measure	Part A: TAK-164 0.004 mg/kg n = 1	Part A: TAK-164 0.008 mg/kg n = 1	Part A: TAK-164 0.016 mg/kg n = 1	Part A: TAK-164 0.032 mg/kg n = 5	Part A: TAK-164 0.064 mg/kg n = 7	Part A: TAK-164 0.12 mg/kg n = 7	Part A: TAK-164 0.16 mg/kg n = 2	Part A: TAK-164 0.19 mg/kg n = 3	Part A: TAK-164 0.25 mg/kg n = 3	Part A: TAK-164 0.32 mg/kg n = 1
Value	0	0	0	0	0	0	0	1	2	0

Population analysed: The safety population was defined as all participants who received at least 1 dose of study drug.

Primary outcome: Percentage of Participants With Adverse Events (AEs)

Time frame: From first dose of study drug up to 30 days following the last dose of study drug (up to 22 months). Number. Unit: percentage of participants

Measure	Part A: TAK-164 0.004 mg/kg n = 1	Part A: TAK-164 0.008 mg/kg n = 1	Part A: TAK-164 0.016 mg/kg n = 1	Part A: TAK-164 0.032 mg/kg n = 5	Part A: TAK-164 0.064 mg/kg n = 7	Part A: TAK-164 0.12 mg/kg n = 7	Part A: TAK-164 0.16 mg/kg n = 2	Part A: TAK-164 0.19 mg/kg n = 3	Part A: TAK-164 0.25 mg/kg n = 3	Part A: TAK-164 0.32 mg/kg n = 1
Value	100	100	100	100	100	100	100	100	100	100

Population analysed: The safety population was defined as all participants who received at least 1 dose of study drug.

Primary outcome: Percentage of Participants With Grade 3 or Above AEs

Time frame: From first dose of study drug up to 30 days following the last dose of study drug (up to 22 months). Number. Unit: percentage of participants

Measure	Part A: TAK-164 0.004 mg/kg n = 1	Part A: TAK-164 0.008 mg/kg n = 1	Part A: TAK-164 0.016 mg/kg n = 1	Part A: TAK-164 0.032 mg/kg n = 5	Part A: TAK-164 0.064 mg/kg n = 7	Part A: TAK-164 0.12 mg/kg n = 7	Part A: TAK-164 0.16 mg/kg n = 2	Part A: TAK-164 0.19 mg/kg n = 3	Part A: TAK-164 0.25 mg/kg n = 3	Part A: TAK-164 0.32 mg/kg n = 1
Value	0	100	100	60	14.3	71.4	50.0	100	100	0

Population analysed: The safety population was defined as all participants who received at least 1 dose of study drug.

Primary outcome: Percentage of Participants With Drug-related AEs

Time frame: From first dose of study drug up to 30 days following the last dose of study drug (up to 22 months). Number. Unit: percentage of participants

Measure	Part A: TAK-164 0.004 mg/kg n = 1	Part A: TAK-164 0.008 mg/kg n = 1	Part A: TAK-164 0.016 mg/kg n = 1	Part A: TAK-164 0.032 mg/kg n = 5	Part A: TAK-164 0.064 mg/kg n = 7	Part A: TAK-164 0.12 mg/kg n = 7	Part A: TAK-164 0.16 mg/kg n = 2	Part A: TAK-164 0.19 mg/kg n = 3	Part A: TAK-164 0.25 mg/kg n = 3	Part A: TAK-164 0.32 mg/kg n = 1
Value	100	0	100	100	85.7	71.4	50.0	66.7	66.7	100

Population analysed: The safety population was defined as all participants who received at least 1 dose of study drug.

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: Treatment-emergent adverse events are adverse events that started after the first dose of study drug up to 30 days following the last dose of study drug (up to 22 months). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part A: TAK-164 0.004 mg/kg	0 of 1 (0%)	1 of 1 (100%)	0 of 1
Part A: TAK-164 0.008 mg/kg	1 of 1 (100%)	1 of 1 (100%)	0 of 1
Part A: TAK-164 0.016 mg/kg	0 of 1 (0%)	1 of 1 (100%)	0 of 1
Part A: TAK-164 0.032 mg/kg	3 of 5 (60%)	5 of 5 (100%)	0 of 5
Part A: TAK-164 0.064 mg/kg	0 of 7 (0%)	7 of 7 (100%)	1 of 7
Part A: TAK-164 0.12 mg/kg	3 of 7 (42.9%)	6 of 7 (85.7%)	0 of 7
Part A: TAK-164 0.16 mg/kg	1 of 2 (50%)	2 of 2 (100%)	0 of 2
Part A: TAK-164 0.19 mg/kg	2 of 3 (66.7%)	3 of 3 (100%)	1 of 3
Part A: TAK-164 0.25 mg/kg	2 of 3 (66.7%)	3 of 3 (100%)	0 of 3
Part A: TAK-164 0.32 mg/kg	0 of 1 (0%)	1 of 1 (100%)	0 of 1

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 36738333Kim R, Leal AD, Parikh A, Ryan DP, Wang S, Bahamon B, Gupta N, Moss A, Pye J, Miao H, Inguilizian H, Cleary JM. A phase I, first-in-human study of TAK-164, an antibody-drug conjugate, in patients with advanced gastrointestinal cancers expressing guanylyl cyclase C. Cancer Chemother Pharmacol. 2023 Apr;91(4):291-300. doi: 10.1007/s00280-023-04507-w. Epub 2023 Feb 4.
Derived from this study: PubMed 32788205Abu-Yousif AO, Cvet D, Gallery M, Bannerman BM, Ganno ML, Smith MD, Lai KC, Keating TA, Stringer B, Kamali A, Eng K, Koseoglu S, Zhu A, Xia CQ, Landen MS, Borland M, Robertson R, Bolleddula J, Qian MG, Fretland J, Veiby OP. Preclinical Antitumor Activity and Biodistribution of a Novel Anti-GCC Antibody-Drug Conjugate in Patient-derived Xenografts. Mol Cancer Ther. 2020 Oct;19(10):2079-2088. doi: 10.1158/1535-7163.MCT-19-1102. Epub 2020 Aug 11.
Individual participant dataSharing planned: Yes. Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

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.

Medical Director study director

Millennium Pharmaceuticals, Inc.

4 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 13 inclusion and 8 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 22 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 22 Mar 2021). 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 Dose-limiting Toxicities (DLTs) (time frame: Baseline up to Month 22). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03449030, which also lists 2 linked publications.

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 22 Mar 2021.