Clinical Trials /

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

NCT03449030

Description:

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.

Related Conditions:
  • Digestive System Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: TAK-164-1001
  • SECONDARY ID: U1111-1207-9923
  • SECONDARY ID: 2018-002214-12
  • NCT ID: NCT03449030

Conditions

  • Gastrointestinal Neoplasms; Esophageal, Stomach, Pancreas, Colon Neoplasms; Malignant Tumors of Digestive Organ; Advanced Gastrointestinal Malignancies

Interventions

DrugSynonymsArms
TAK-164Part A Escalation Stage: TAK-164 Q3W
89Zr-TAK-164Part C Imaging Substudy: 89Zr-TAK-164 and TAK-164

Purpose

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

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Part A Escalation Stage: TAK-164 Q3WExperimentalTAK-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.
  • TAK-164
Part B Expansion Stage: TAK-164 Q3WExperimentalTAK-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.
  • TAK-164
Part C Imaging Substudy: 89Zr-TAK-164 and TAK-164Experimental89Zr-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.
  • TAK-164
  • 89Zr-TAK-164

Eligibility Criteria

        Inclusion Criteria:

          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
             indications).

             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
             drug.

          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
             (mL/min).

          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
             criteria:

         11. At least 1 extrahepatic metastatic lesion >=2 centimeter (cm) in the longest diameter.

        Exclusion Criteria:

          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
             resection.

          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
             (DILI).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with Dose-limiting Toxicities (DLTs)
Time Frame:Up to 36 months
Safety Issue:
Description:DLTs will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.

Secondary Outcome Measures

Measure:Cmax: Maximum Observed Plasma Concentration for TAK-164
Time Frame:Cycle 1 and 2 Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose [Cycle length is equal to (=) 21 days]
Safety Issue:
Description:
Measure:Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-164
Time Frame:Cycle 1 and 2 Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose (Cycle length = 21 days)
Safety Issue:
Description:
Measure:AUClast: Area Under the Plasma Concentration-time Curve from Time 0 to Time of Last Quantifiable Concentration for TAK-164
Time Frame:Cycle 1 and 2 Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose (Cycle length = 21 days)
Safety Issue:
Description:
Measure:Ctrough: Observed Concentration Measured at the end of a Dosing Interval for TAK-164
Time Frame:Cycle 1 and 2 Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose (Cycle length = 21 days)
Safety Issue:
Description:
Measure:Overall Response Rate (ORR)
Time Frame:Up to 36 months
Safety Issue:
Description:ORR is defined as the percentage of participants with complete response (CR), or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Measure:Disease Control Rate (DCR)
Time Frame:Up to 36 months
Safety Issue:
Description:DCR is defined as the percentage of participants with CR, PR or stable disease (SD) with a minimum of 12 weeks duration. DCR will be assessed based on RECIST version 1.1 criteria.
Measure:Duration of Response (DOR)
Time Frame:Up to 36 months
Safety Issue:
Description:DOR is defined as the time from the date of first documentation of a response to the date of first documentation of disease progression (PD) according to RECIST version 1.1 criteria.
Measure:Progression-free Survival (PFS)
Time Frame:Up to 36 months
Safety Issue:
Description:PFS is defined as the time from the date of first study drug administration to the date of first documentation of PD or death. PFS will be assessed based on RECIST version 1.1 criteria.
Measure:Number of Participants with Antidrug Antibody (ADA) Levels in Serum
Time Frame:Up to 36 months
Safety Issue:
Description:
Measure:Part C: Mean Standardized Patient-level Biodistribution Value of Zicronium 89-labeled-TAK-164 (89Zr-TAK-164)
Time Frame:Day -14: at 1 hour post 89Zr-TAK-164 end of infusion (EOI), Days -12 and -10, and Days 3 and 5 (Cycle 1): post 89Zr-TAK-164 EOI (Cycle length = 21 days)
Safety Issue:
Description:
Measure:Part C: Relationship Between 89Zr-TAK-164 and Zr-TAK-164 Positron Emission Tomography (PET) Scan
Time Frame:Day -14: at 1 hour post 89Zr-TAK-164 EOI, Days -12 and -10, and Days 3 and 5 (Cycle 1): post 89Zr-TAK-164 EOI (Cycle length = 21 days)
Safety Issue:
Description:
Measure:Part C: Mean Standardized Uptake Value (SUV) of 89Zr-TAK-164 Uptake in Tumor Lesions
Time Frame:Days -12 and -10, and Days 3 and 5 (Cycle 1): post 89Zr-TAK-164 EOI (Cycle length = 21 days)
Safety Issue:
Description:
Measure:Part C: Relationship between 89Zr-TAK-164 uptake in Tumor Lesions and Computed Tomography (CT) or 18-flurodeoxyglycose (18F-FDG) positron emission tomography (PET)
Time Frame:Days -12 and -10, and Days 3 and 5 (Cycle 1): post 89Zr-TAK-164 EOI (Cycle length = 21 days)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Millennium Pharmaceuticals, Inc.

Trial Keywords

  • Drug Therapy

Last Updated

November 14, 2019