CClinicalTrials.gg
Sign In
TerminatedNCT03449030Updated Mar 22, 2021Results posted

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

A Phase 1 interventional study of TAK-164 and 89Zr-TAK-164 in Gastrointestinal Neoplasms; Esophageal, Stomach, Pancreas, Colon Neoplasms; Malignant Tumors of Digestive Organ; Advanced Gastrointestinal Malignancies, sponsored by Millennium Pharmaceuticals, Inc.. Terminated at 4 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-03-22.

Sponsored by Millennium Pharmaceuticals, Inc. · Phase 1, Interventional, and Other

Why this study was terminated
Insufficient clinical benefit to participants at the selected recommended phase 2 (RP2D) dose in Part A.
Phase
Phase 1
Study type
Interventional
Enrollment
31
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study 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 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.

02

Conditions studied

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

Keywords

  • Drug Therapy
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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).
04

Study design

Phase
Phase 1
Primary purpose
Other
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
31 participants (actual)

Study arms

  • Experimental
    Part A Escalation Stage: TAK-164 Q3W

    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.

    Drug: TAK-164

  • Experimental
    Part B Expansion Stage: TAK-164 Q3W

    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.

    Drug: TAK-164

  • Experimental
    Part C Imaging Substudy: 89Zr-TAK-164 and TAK-164

    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.

    Drug: TAK-164 · Drug: 89Zr-TAK-164

Interventions

  • DrugTAK-164

    TAK-164 intravenous infusion.

  • Drug89Zr-TAK-164

    89Zr-TAK-164 intravenous infusion

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Baseline up to Month 22

  2. 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)

  3. 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.

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

  4. 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)

  5. 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.

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

  6. 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)

  7. 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)

  8. Recommended Phase 2 Dose (RP2D) of TAK-164

    RP2D was the highest safe dose that could be applied to the expansion phase.

    Time frame: Baseline up to Month 22

Secondary outcomes

  1. 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)

  2. 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)

  3. 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)

  4. 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)

  5. 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.

    Time frame: From start of study treatment until the start of subsequent anti cancer therapy ( up to Month 22)

  6. 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.

    Time frame: Baseline up to Month 22

  7. 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.

    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)

  8. 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.

    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)

  9. Number of Participants With Positive Antidrug Antibody (ADA) Levels in Serum

    Time frame: Baseline up to Month 22

06

Results

Posted Mar 22, 2021

Participant flow

Participants took part in the study at 5 investigative sites in the United States from 23 April 2018 to 27 February 2020.

Participant flow — Overall Study
MilestonePart A: TAK-164 0.004 mg/kgPart A: TAK-164 0.008 mg/kgPart A: TAK-164 0.016 mg/kgPart A: TAK-164 0.032 mg/kgPart A: TAK-164 0.064 mg/kgPart A: TAK-164 0.12 mg/kgPart A: TAK-164 0.16 mg/kgPart A: TAK-164 0.19 mg/kgPart A: TAK-164 0.25 mg/kgPart A: TAK-164 0.32 mg/kg
Started1115772331
Completed0000000000
Not completed1115772331
Withdrew: Withdrawal by subject0001111200
Withdrew: Symptomatic deterioration0100011020
Withdrew: Progressive disease1014530111
Withdrew: Adverse event0000020000
Withdrew: Death0000100000

Outcome measures

PrimaryNumber 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.

Time frame:
Baseline up to Month 22
Reported as:
Count of participants · Participants
Number of Participants With Dose-limiting Toxicities (DLTs)
ParticipantsPart A: TAK-164 0.004 mg/kgPart A: TAK-164 0.008 mg/kgPart A: TAK-164 0.016 mg/kgPart A: TAK-164 0.032 mg/kgPart A: TAK-164 0.064 mg/kgPart A: TAK-164 0.12 mg/kgPart A: TAK-164 0.16 mg/kgPart A: TAK-164 0.19 mg/kgPart A: TAK-164 0.25 mg/kgPart A: TAK-164 0.32 mg/kg
Number of Participants With Dose-limiting Toxicities (DLTs)0000000120
PrimaryPercentage 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)
Reported as:
Number · percentage of participants
Percentage of Participants With Adverse Events (AEs)
percentage of participantsPart A: TAK-164 0.004 mg/kgPart A: TAK-164 0.008 mg/kgPart A: TAK-164 0.016 mg/kgPart A: TAK-164 0.032 mg/kgPart A: TAK-164 0.064 mg/kgPart A: TAK-164 0.12 mg/kgPart A: TAK-164 0.16 mg/kgPart A: TAK-164 0.19 mg/kgPart A: TAK-164 0.25 mg/kgPart A: TAK-164 0.32 mg/kg
Percentage of Participants With Adverse Events (AEs)100100100100100100100100100100
PrimaryPercentage 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.

Time frame:
From first dose of study drug up to 30 days following the last dose of study drug (up to 22 months)
Reported as:
Number · percentage of participants
Percentage of Participants With Grade 3 or Above AEs
percentage of participantsPart A: TAK-164 0.004 mg/kgPart A: TAK-164 0.008 mg/kgPart A: TAK-164 0.016 mg/kgPart A: TAK-164 0.032 mg/kgPart A: TAK-164 0.064 mg/kgPart A: TAK-164 0.12 mg/kgPart A: TAK-164 0.16 mg/kgPart A: TAK-164 0.19 mg/kgPart A: TAK-164 0.25 mg/kgPart A: TAK-164 0.32 mg/kg
Percentage of Participants With Grade 3 or Above AEs01001006014.371.450.01001000
PrimaryPercentage 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)
Reported as:
Number · percentage of participants
Percentage of Participants With Drug-related AEs
percentage of participantsPart A: TAK-164 0.004 mg/kgPart A: TAK-164 0.008 mg/kgPart A: TAK-164 0.016 mg/kgPart A: TAK-164 0.032 mg/kgPart A: TAK-164 0.064 mg/kgPart A: TAK-164 0.12 mg/kgPart A: TAK-164 0.16 mg/kgPart A: TAK-164 0.19 mg/kgPart A: TAK-164 0.25 mg/kgPart A: TAK-164 0.32 mg/kg
Percentage of Participants With Drug-related AEs100010010085.771.450.066.766.7100
PrimaryPercentage 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.

Time frame:
From first dose of study drug up to 30 days following the last dose of study drug (up to 22 months)
Reported as:
Number · percentage of participants
Percentage of Participants With Drug-related Grade 3 or Above AEs
percentage of participantsPart A: TAK-164 0.004 mg/kgPart A: TAK-164 0.008 mg/kgPart A: TAK-164 0.016 mg/kgPart A: TAK-164 0.032 mg/kgPart A: TAK-164 0.064 mg/kgPart A: TAK-164 0.12 mg/kgPart A: TAK-164 0.16 mg/kgPart A: TAK-164 0.19 mg/kgPart A: TAK-164 0.25 mg/kgPart A: TAK-164 0.32 mg/kg
Percentage of Participants With Drug-related Grade 3 or Above AEs0010020.014.342.950.033.366.70
PrimaryPercentage 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)
Reported as:
Number · percentage of participants
Percentage of Participants With Serious Adverse Events (SAEs)
percentage of participantsPart A: TAK-164 0.004 mg/kgPart A: TAK-164 0.008 mg/kgPart A: TAK-164 0.016 mg/kgPart A: TAK-164 0.032 mg/kgPart A: TAK-164 0.064 mg/kgPart A: TAK-164 0.12 mg/kgPart A: TAK-164 0.16 mg/kgPart A: TAK-164 0.19 mg/kgPart A: TAK-164 0.25 mg/kgPart A: TAK-164 0.32 mg/kg
Percentage of Participants With Serious Adverse Events (SAEs)0100060042.950.066.766.70
PrimaryPercentage 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)
Reported as:
Number · percentage of participants
Percentage of Participants With AEs Leading to Discontinuation
percentage of participantsPart A: TAK-164 0.004 mg/kgPart A: TAK-164 0.008 mg/kgPart A: TAK-164 0.016 mg/kgPart A: TAK-164 0.032 mg/kgPart A: TAK-164 0.064 mg/kgPart A: TAK-164 0.12 mg/kgPart A: TAK-164 0.16 mg/kgPart A: TAK-164 0.19 mg/kgPart A: TAK-164 0.25 mg/kgPart A: TAK-164 0.32 mg/kg
Percentage of Participants With AEs Leading to Discontinuation0000028.60033.30
SecondaryCmax: 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)

No measurements were reported for this outcome.

SecondaryTmax: 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)

No measurements were reported for this outcome.

SecondaryAUClast: 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)

No measurements were reported for this outcome.

SecondaryCtrough: 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)

No measurements were reported for this outcome.

SecondaryOverall 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.

Time frame:
From start of study treatment until the start of subsequent anti cancer therapy ( up to Month 22)
Reported as:
Number · percentage of participants
Overall Response Rate (ORR)
percentage of participantsPart A: TAK-164 0.004 mg/kgPart A: TAK-164 0.008 mg/kgPart A: TAK-164 0.016 mg/kgPart A: TAK-164 0.032 mg/kgPart A: TAK-164 0.064 mg/kgPart A: TAK-164 0.12 mg/kgPart A: TAK-164 0.16 mg/kgPart A: TAK-164 0.19 mg/kgPart A: TAK-164 0.25 mg/kgPart A: TAK-164 0.32 mg/kg
Overall Response Rate (ORR)0 (0.0 to 97.5)100 (2.5 to 100.0)0 (0.0 to 97.5)0 (0.0 to 52.2)0 (0.0 to 45.9)0 (0.0 to 52.2)0 (0.0 to 84.2)0 (0.0 to 84.2)0 (0.0 to 97.5)0 (0.0 to 97.5)
SecondaryDisease 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.

Time frame:
Baseline up to Month 22
Reported as:
Number · percentage of participants
Disease Control Rate (DCR)
percentage of participantsPart A: TAK-164 0.004 mg/kgPart A: TAK-164 0.008 mg/kgPart A: TAK-164 0.016 mg/kgPart A: TAK-164 0.032 mg/kgPart A: TAK-164 0.064 mg/kgPart A: TAK-164 0.12 mg/kgPart A: TAK-164 0.16 mg/kgPart A: TAK-164 0.19 mg/kgPart A: TAK-164 0.25 mg/kgPart A: TAK-164 0.32 mg/kg
Disease Control Rate (DCR)100 (2.5 to 100.0)100 (2.5 to 100.0)100 (2.5 to 100.0)40.0 (5.3 to 85.3)50.0 (11.8 to 88.2)40.0 (5.3 to 85.3)50.0 (1.3 to 98.7)50.0 (1.3 to 98.7)0 (0.0 to 97.5)0 (0.0 to 97.5)
SecondaryDuration 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.

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)
Reported as:
Median · months
Duration of Response (DOR)
monthsPart A: TAK-164 0.004 mg/kgPart A: TAK-164 0.008 mg/kgPart A: TAK-164 0.016 mg/kgPart A: TAK-164 0.032 mg/kgPart A: TAK-164 0.064 mg/kgPart A: TAK-164 0.12 mg/kgPart A: TAK-164 0.16 mg/kgPart A: TAK-164 0.19 mg/kgPart A: TAK-164 0.25 mg/kgPart A: TAK-164 0.32 mg/kg
Duration of Response (DOR)—NA (NA to NA)————————
SecondaryProgression-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.

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)
Reported as:
Median · months
Progression-free Survival (PFS)
monthsPart A: TAK-164 0.004 mg/kgPart A: TAK-164 0.008 mg/kgPart A: TAK-164 0.016 mg/kgPart A: TAK-164 0.032 mg/kgPart A: TAK-164 0.064 mg/kgPart A: TAK-164 0.12 mg/kgPart A: TAK-164 0.16 mg/kgPart A: TAK-164 0.19 mg/kgPart A: TAK-164 0.25 mg/kgPart A: TAK-164 0.32 mg/kg
Progression-free Survival (PFS)2.79 (NA to NA)—6.24 (NA to NA)1.35 (0.59 to NA)1.91 (1.22 to 3.48)1.58 (1.08 to 1.58)1.41 (NA to NA)1.81 (1.25 to 2.37)1.05 (NA to NA)1.18 (NA to NA)
SecondaryNumber of Participants With Positive Antidrug Antibody (ADA) Levels in Serum
Time frame:
Baseline up to Month 22
Reported as:
Count of participants · Participants
Number of Participants With Positive Antidrug Antibody (ADA) Levels in Serum
ParticipantsPart A: TAK-164 0.004 mg/kgPart A: TAK-164 0.008 mg/kgPart A: TAK-164 0.016 mg/kgPart A: TAK-164 0.032 mg/kgPart A: TAK-164 0.064 mg/kgPart A: TAK-164 0.12 mg/kgPart A: TAK-164 0.16 mg/kgPart A: TAK-164 0.19 mg/kgPart A: TAK-164 0.25 mg/kgPart A: TAK-164 0.32 mg/kg
Number of Participants With Positive Antidrug Antibody (ADA) Levels in Serum0000010000
PrimaryRecommended Phase 2 Dose (RP2D) of TAK-164

RP2D was the highest safe dose that could be applied to the expansion phase.

Time frame:
Baseline up to Month 22
Reported as:
Number · mg/kg
Recommended Phase 2 Dose (RP2D) of TAK-164
mg/kgPart A: TAK-164
Recommended Phase 2 Dose (RP2D) of TAK-1640.064

Adverse events

Collected over 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). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Part A: TAK-164 0.004 mg/kg0/1 (0%)0/1 (0%)1/1 (100%)
Part A: TAK-164 0.008 mg/kg0/1 (0%)1/1 (100%)1/1 (100%)
Part A: TAK-164 0.016 mg/kg0/1 (0%)0/1 (0%)1/1 (100%)
Part A: TAK-164 0.032 mg/kg0/5 (0%)3/5 (60%)5/5 (100%)
Part A: TAK-164 0.064 mg/kg1/7 (14.3%)0/7 (0%)7/7 (100%)
Part A: TAK-164 0.12 mg/kg0/7 (0%)3/7 (42.9%)6/7 (85.7%)
Part A: TAK-164 0.16 mg/kg0/2 (0%)1/2 (50%)2/2 (100%)
Part A: TAK-164 0.19 mg/kg1/3 (33.3%)2/3 (66.7%)3/3 (100%)
Part A: TAK-164 0.25 mg/kg0/3 (0%)2/3 (66.7%)3/3 (100%)
Part A: TAK-164 0.32 mg/kg0/1 (0%)0/1 (0%)1/1 (100%)
Most frequent serious events
Showing 10 of 17
Most frequent serious events
EventPart A: TAK-164 0.004 mg/kgPart A: TAK-164 0.008 mg/kgPart A: TAK-164 0.016 mg/kgPart A: TAK-164 0.032 mg/kgPart A: TAK-164 0.064 mg/kgPart A: TAK-164 0.12 mg/kgPart A: TAK-164 0.16 mg/kgPart A: TAK-164 0.19 mg/kgPart A: TAK-164 0.25 mg/kgPart A: TAK-164 0.32 mg/kg
ArrhythmiaCardiac disorders0/11/10/10/50/70/70/20/30/30/1
Pleural effusionRespiratory, thoracic and mediastinal disorders0/11/10/10/50/70/70/20/30/30/1
VomitingGastrointestinal disorders0/10/10/10/50/70/71/20/30/30/1
Abdominal painGastrointestinal disorders0/10/10/10/50/71/70/21/31/30/1
NauseaGastrointestinal disorders0/10/10/10/50/70/70/20/31/30/1
ProctalgiaGastrointestinal disorders0/10/10/10/50/70/70/21/30/30/1
Hepatic failureHepatobiliary disorders0/10/10/10/50/70/70/20/31/30/1
HyperbilirubinaemiaHepatobiliary disorders0/10/10/10/50/70/70/21/30/30/1
Platelet count decreasedInvestigations0/10/10/10/50/70/70/20/31/30/1
PneumoniaInfections and infestations0/10/10/10/50/70/70/21/30/30/1
Most frequent other events
Showing 10 of 115
Most frequent other events
EventPart A: TAK-164 0.004 mg/kgPart A: TAK-164 0.008 mg/kgPart A: TAK-164 0.016 mg/kgPart A: TAK-164 0.032 mg/kgPart A: TAK-164 0.064 mg/kgPart A: TAK-164 0.12 mg/kgPart A: TAK-164 0.16 mg/kgPart A: TAK-164 0.19 mg/kgPart A: TAK-164 0.25 mg/kgPart A: TAK-164 0.32 mg/kg
Abdominal painGastrointestinal disorders0/11/11/13/52/70/71/21/31/30/1
NauseaGastrointestinal disorders0/10/11/12/52/73/70/21/31/30/1
VomitingGastrointestinal disorders0/10/11/12/53/71/71/20/32/30/1
Dry mouthGastrointestinal disorders0/10/10/10/50/72/70/20/30/31/1
FatigueGeneral disorders0/10/11/14/54/73/70/22/32/30/1
PyrexiaGeneral disorders0/11/10/11/51/71/70/20/32/30/1
ChillsGeneral disorders0/11/10/11/51/71/70/20/30/30/1
Oedema peripheralGeneral disorders0/11/10/10/51/70/70/20/32/30/1
Platelet count decreasedInvestigations0/10/11/15/53/75/71/21/33/30/1
Aspartate aminotransferase increasedInvestigations0/10/10/13/51/74/70/21/33/30/1

Baseline characteristics

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

Age, Continuous
Age, Continuous(years)Part A: TAK-164 0.004 mg/kgPart A: TAK-164 0.008 mg/kgPart A: TAK-164 0.016 mg/kgPart A: TAK-164 0.032 mg/kgPart A: TAK-164 0.064 mg/kgPart A: TAK-164 0.12 mg/kgPart A: TAK-164 0.16 mg/kgPart A: TAK-164 0.19 mg/kgPart A: TAK-164 0.25 mg/kgPart A: TAK-164 0.32 mg/kgTotal
Mean72.0 ± NA52.0 ± NA59.0 ± NA55.2 ± 8.1457.1 ± 8.3648.0 ± 13.1153.0 ± 14.1465.3 ± 3.2148.0 ± 3.6139.0 ± NA54.2 ± 10.59
Sex: Female, Male
Sex: Female, Male(Participants)Part A: TAK-164 0.004 mg/kgPart A: TAK-164 0.008 mg/kgPart A: TAK-164 0.016 mg/kgPart A: TAK-164 0.032 mg/kgPart A: TAK-164 0.064 mg/kgPart A: TAK-164 0.12 mg/kgPart A: TAK-164 0.16 mg/kgPart A: TAK-164 0.19 mg/kgPart A: TAK-164 0.25 mg/kgPart A: TAK-164 0.32 mg/kgTotal
Female111444110118
Male000133123013
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Part A: TAK-164 0.004 mg/kgPart A: TAK-164 0.008 mg/kgPart A: TAK-164 0.016 mg/kgPart A: TAK-164 0.032 mg/kgPart A: TAK-164 0.064 mg/kgPart A: TAK-164 0.12 mg/kgPart A: TAK-164 0.16 mg/kgPart A: TAK-164 0.19 mg/kgPart A: TAK-164 0.25 mg/kgPart A: TAK-164 0.32 mg/kgTotal
Hispanic or Latino00000000000
Not Hispanic or Latino111467233129
Unknown or Not Reported00011000002
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Part A: TAK-164 0.004 mg/kgPart A: TAK-164 0.008 mg/kgPart A: TAK-164 0.016 mg/kgPart A: TAK-164 0.032 mg/kgPart A: TAK-164 0.064 mg/kgPart A: TAK-164 0.12 mg/kgPart A: TAK-164 0.16 mg/kgPart A: TAK-164 0.19 mg/kgPart A: TAK-164 0.25 mg/kgPart A: TAK-164 0.32 mg/kgTotal
American Indian or Alaska Native00000000000
Asian00000101013
Native Hawaiian or Other Pacific Islander00000000000
Black or African American00001100002
White111465223025
More than one race00000000000
Unknown or Not Reported00010000001
Region of Enrollment
Region of Enrollment(Participants)Part A: TAK-164 0.004 mg/kgPart A: TAK-164 0.008 mg/kgPart A: TAK-164 0.016 mg/kgPart A: TAK-164 0.032 mg/kgPart A: TAK-164 0.064 mg/kgPart A: TAK-164 0.12 mg/kgPart A: TAK-164 0.16 mg/kgPart A: TAK-164 0.19 mg/kgPart A: TAK-164 0.25 mg/kgPart A: TAK-164 0.32 mg/kgTotal
United States111577233131
07

Study locations

4 sites
  • University of Colorado Cancer Center
    Aurora, Colorado 80045, United States
  • Moffitt Cancer Center
    Tampa, Florida 33612, United States
  • Massachusetts General Hospital
    Boston, Massachusetts 02114-2621, United States
  • SCRI - Tennessee Oncology Nashville - Southern Hills Clinic
    Nashville, Tennessee 37205, United States
08

References and documents

Publications

  • 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 documents

  • Study protocol · Sep 4, 2019
  • Statistical analysis plan · May 8, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: 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.

Supporting information: Study protocol, Sap, Icf, Csr

09

Registry details

Key details

Study ID
NCT03449030
Lead sponsor
Millennium Pharmaceuticals, Inc.
Responsible party
Sponsor
First posted
Feb 28, 2018
Start date
Apr 23, 2018
Primary completion
Feb 27, 2020
Completion
Feb 27, 2020
Results posted
Mar 22, 2021
Last update
Mar 22, 2021

Study contacts

Medical Director
study director · Millennium Pharmaceuticals, Inc.

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is terminated, as verified in Feb 2021. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Gastrointestinal Neoplasms→

Other studies from this sponsor

Millennium Pharmaceuticals, Inc.

Start the discussion