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.
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.
1. 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
o Part B of the study will be limited to participants with 2 or 3 prior lines of
systemic standard of care therapy.
2. Male or female participants 18 years or older.
3. 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
4. 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.
5. Adequate renal function as defined by creatinine CL >= 60 milliliter per minute
6. Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1.
7. Life expectancy of at least 12 weeks.
8. Completion of prior chemotherapy, biologic therapy, immunotherapy, or radiation
therapy at least 4 weeks prior to enrollment.
9. Resolution of all toxic effects of prior treatments (except alopecia) to Grade <=1 NCI
CTCAE, version 5.
10. 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
11. At least 1 extrahepatic metastatic lesion >=2 centimeter (cm) in the longest diameter.
1. Treatment with anticancer chemotherapy or biologic therapy or with an experimental
anticancer agent within 28 days of the initial dose of study drug.
2. 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
3. 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.
4. 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.
5. 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).
6. Participant has concurrent alcohol abuse or a history of drug-induced liver injury