Clinical Trials /

A Study of TAK-102 in Adult Patients With GPC3-Expressing Previously Treated Solid Tumors

NCT04405778

Description:

The purpose of this study is to evaluate the safety and tolerability of TAK-102 and to determine the recommended phase 2 dose (RP2D) of TAK-102.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of TAK-102 in Adult Patients With GPC3-Expressing Previously Treated Solid Tumors
  • Official Title: An Open-Label, Dose Escalation, Phase 1, First-in-Human Study of TAK-102 in Adult Patients With GPC3-Expressing Previously Treated Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: TAK-102-1501
  • SECONDARY ID: U1111-1247-6429
  • SECONDARY ID: JapicCTI-205300
  • NCT ID: NCT04405778

Conditions

  • Solid Tumors

Interventions

DrugSynonymsArms
TAK-102TAK-102 Cohort 1

Purpose

The purpose of this study is to evaluate the safety and tolerability of TAK-102 and to determine the recommended phase 2 dose (RP2D) of TAK-102.

Detailed Description

      The drug being tested in this study is called TAK-102. TAK-102 is being tested to treat
      people who have GPC3-expressing previously treated solid tumors. This study will look at the
      safety and tolerability of TAK-102 and will determine the RP2D of TAK-102.

      The study will enroll approximately 14 participants, with a maximum of 18 participants.
      Participants will be assigned to 1 of the 3 treatment groups (dose cohorts) and dose
      escalation will be conducted in this study:

        -  Cohort 1: 1 × 10^7 CAR (+) cells/body [starting dose].

        -  Cohort 2: 1 × 10^8 CAR (+) cells/body.

        -  Cohort 3: 1 × 10^9 CAR (+) cells/body.

      In case Cohort 1 is not tolerable, the dose level will be de-escalated to Cohort -1: 3 × 10^6
      CAR (+) cells/body. Dose level(s) between planned cohorts and/or other dosing schedules may
      also be tested.

      This study consists of the Screening, Pretreatment, and Treatment and Primary Follow-up
      phases. In Treatment and Primary Follow-up phases, all participants will be asked to receive
      a single intravenous infusion of TAK-102 and administration of TAK-102 will continue up to
      Month 12.

      This multi-center trial will be conducted in Japan. The overall time to participate in this
      study is 15 years as a maximum including planned long-term follow-up study (the 12-month
      Treatment and Primary Follow-up and the 14-year Secondary Follow-up phases in another study).
      Participants will make multiple visits to the clinic and be hospitalized for at least 28 days
      to receive treatment with TAK-102 followed by a recovery period.
    

Trial Arms

NameTypeDescriptionInterventions
TAK-102 Cohort 1ExperimentalTAK-102, 1 × 10^7 Chimeric antigen receptor (CAR) (+) cells/body as a starting dose, intravenous infusion, will be administered at approximately 5 mL/min and completed within 30 minutes.
  • TAK-102
TAK-102 Cohort 2ExperimentalTAK-102, 1 × 10^8 CAR (+) cells/body as a starting dose, intravenous infusion, will be administered at approximately 5 mL/min and completed within 30 minutes.
  • TAK-102
TAK-102 Cohort 3ExperimentalTAK-102, 1 × 10^9 CAR (+) cells/body as a starting dose, intravenous infusion, will be administered at approximately 5 mL/min and completed within 30 minutes.
  • TAK-102

Eligibility Criteria

        Inclusion Criteria:

          1. Male or female participants aged ≥18 years at the time of signing informed consent.

          2. Participants must have a diagnosis of solid tumors.

          3. Participants with solid tumor who are refractory or intolerant to standard treatments.

          4. GPC3-expression must be determined on the tumor locally by IHC using a validated
             assay, scoring and staining confirmed by the sponsor. Fresh biopsy sample must be used
             for eligibility assessment unless archived biopsy sample obtained within 6 months
             prior to leukapheresis procedures is available.

          5. Life expectancy ≥12 weeks.

          6. ECOG performance status of 0 or 1.

          7. Adequate organ function as confirmed by clinical laboratory values as specified below:

               1. Total bilirubin must be <1.5 × the upper limit of the normal range (ULN). Total
                  bilirubin may be elevated up to 3 × ULN if the elevation can be reasonably
                  ascribed to the presence of metastatic disease in the liver.

               2. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) must be <3 ×
                  ULN. AST and ALT may be elevated up to 5 × ULN if the elevation can be reasonably
                  ascribed to the presence of metastatic disease in liver.

               3. Calculated creatinine clearance >50 mL/mins (The Cockcroft-Gault formula).

               4. Hemoglobin must be ≥8 g/dL.

               5. Neutrophil count must be >1000/mm^3.

               6. Absolute lymphocyte count must be >500/mm^3.

               7. Platelet count must be >75,000/mm^3.

               8. Prothrombin time-international normalized ratio must be ≤1.7.

               9. Activated partial thromboplastin time (APTT) must be ≤1.5 × ULN.

          8. Participants must have radiographically measurable disease as defined by RECIST 1.1.

          9. Female participants who:

               1. Are postmenopausal (natural amenorrhea and not due to other medical reasons) for
                  at least 1 year before the screening visit, OR

               2. Are surgically sterile, OR

               3. If they are of childbearing potential, agree to practice 1 highly effective
                  nonhormonal method of contraception and 1 additional effective (barrier) method
                  at the same time, from the time of signing the informed consent through at least
                  12 months following TAK-102 infusion, OR

               4. Agree to practice true abstinence, when this is in line with the preferred and
                  usual lifestyle of the participant.

             Note: Periodic abstinence (eg, calendar, ovulation, symptothermal, postovulation
             methods), withdrawal, spermicides only, and lactational amenorrhea are not acceptable
             methods of contraception.

         10. Male participants, even if surgically sterilized (ie, postvasectomy), who:

               1. Agree to practice effective barrier contraception from the time of signing the
                  informed consent through at least 12 months following TAK-102 infusion, OR

               2. Agree to practice true abstinence, when this is in line with the preferred and
                  usual lifestyle of the participant.

             Note: Periodic abstinence (eg, calendar, ovulation, symptothermal, postovulation
             methods), withdrawal, spermicides only, and lactational amenorrhea are not acceptable
             methods of contraception.

         11. Voluntary written consent must be given before performance of any study-related
             procedures not part of standard medical care, with the understanding that consent may
             be withdrawn by the participant at any time without prejudice to future medical care.

         12. Willingness and ability to comply with scheduled visits and study procedures.

        Exclusion Criteria:

          1. Active systemic infections excluding well-controlled chronic HBV/HCV infections,
             coagulation disorders, or other major medical illnesses including cardiovascular,
             respiratory or immune system, myocardial infarction, cardiac arrhythmias, and
             obstructive/restrictive pulmonary disease.

          2. Participants with known cardiopulmonary disease defined as unstable angina, clinically
             significant arrhythmia, congestive heart failure. A well-controlled atrial
             fibrillation would not be an exclusion whereas uncontrolled atrial fibrillation would
             be an exclusion.

          3. Any serious medical or psychiatric illness that could, in the investigator's opinion,
             potentially interfere with the completion of treatment according to this protocol.

          4. Active, serious infection requiring antibiotics.

          5. Any disease requiring systemic steroid treatment or steroid inhalant.

          6. Any prior use of cell and gene therapy(ies).

          7. Treatment with any investigational products (except for cell or gene therapy) within
             14 days before leukapheresis procedures or 28 days before treatment with
             preconditioning chemotherapy/TAK-102.

          8. Systemic anticancer therapy (including platinum-based chemotherapies and I/O
             therapies) within 14 days before leukapheresis procedures or treatment with
             preconditioning chemotherapy/TAK-102.

          9. Treatment with radiotherapy within 14 days before leukapheresis procedures or
             treatment with preconditioning chemotherapy/TAK-102.

         10. Treatment with major surgery within 28 days before leukapheresis procedures or
             treatment with preconditioning chemotherapy/TAK-102 (minor surgical procedures such as
             catheter placement are not exclusionary criteria).

         11. Previous treatment with any GPC3-targeted therapy.

         12. Any unresolved toxicity greater than Grade 2 from previous anticancer therapy.

         13. Participants with risk of bleeding as judged by the investigator(s).

         14. Presence of central nervous system (CNS) metastasis or other significant neurological
             conditions (participant with CNS metastases that have been effectively treated where
             necessary and stable can be enrolled).

         15. Participants with medically diagnosed past or current hepatic encephalopathy.

         16. Participants with positive human immunodeficiency virus (HIV) and/or human T-cell
             lymphotrophic virus (HTLV) infection.

         17. Participants with clinically significant ascites, which is defined as ascites that are
             physically positive or require intervention (eg, puncture or medication) for control;
             those whose imaging result shows ascites requiring no intervention may be included.

         18. Participants with a history of organ transplantation or awaiting organ
             transplantation.

         19. Participants with severe immediate hypersensitivity to any of the agents including
             cyclophosphamide, fludarabine, ganciclovir, or streptomycin.

         20. Admission or evidence of illicit drug use, drug abuse, or alcohol abuse.

         21. Female participants who are lactating and breastfeeding or have a positive serum
             pregnancy test (urine pregnancy test is allowed before treatment with preconditioning
             chemotherapy and TAK-102).

        Note: Female participants who are lactating will be eligible if they discontinue
        breastfeeding before the treatment with TAK-102.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with First Cycle Dose-Limiting Toxicities (DLTs)
Time Frame:Up to 28 days
Safety Issue:
Description:Toxicity will be evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0. DLT will be defined as any of the events specified in the protocol that are considered by the investigator to be at least possibly related to therapy with study medications.

Secondary Outcome Measures

Measure:Objective response based on the investigator's assessment using study-specific modified Response Evaluation Criteria in Solid Tumors Version 1.1 (ssmRECIST 1.1)
Time Frame:Up to 1 year
Safety Issue:
Description:Objective Response will be assessed by the investigators with ssmRECIST 1.1 and disease response criteria are following; Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Measure:Duration of Response (DOR) as Assessed by the Investigator
Time Frame:Up to 1 year
Safety Issue:
Description:DOR is defined as the time from the date of first documentation of a PR or better (determined by the investigator) to the date of first documentation of progressive disease (PD) for responders (PR or better) per RECIST version 1.1, after the initiation of study treatment. Responders without documentation of PD will be censored at the date of last response assessment that is SD or better. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. PD: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Measure:Disease Control Rate (DCR) as Assessed by the Investigator
Time Frame:Up to 1 year
Safety Issue:
Description:DCR is defined as the percentage of participants who achieve SD or better (determined by the investigator) ≥6 weeks during the study in response-evaluable population per RECIST version 1.1, after the initiation of study treatment. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Measure:Time to Progression as Assessed by the Investigator
Time Frame:Up to 1 year
Safety Issue:
Description:TTP is defined as the time from the date of study drug administration to the date of first documented disease progression by the investigator.
Measure:Progression-Free Survival (PFS) as Assessed by the Investigator
Time Frame:Up to 1 year
Safety Issue:
Description:PFS is defined as the time from the TAK-102 infusion date to the date of disease progression or death from any cause.
Measure:Overall Survival (OS)
Time Frame:Up to 1 year
Safety Issue:
Description:OS is defined as the time from the TAK-102 infusion to the date of death from any cause.
Measure:Maximum (Peak) Observed in Peripheral Blood Drug Concentration after Single Dose Administration (Cmax) Evaluated by CAR Copy Number
Time Frame:Up to 1 year; Pre-dose and multiple time points (Day 1,2,3,4,5,6,7,9,11,14,17,21.28, Month 2 to 6 and Month 7-12) post-dose after the intravenous infusion
Safety Issue:
Description:
Measure:Time of First Occurrence of Maximum Observed Plasma Concentration (Tmax) Evaluated by CAR Copy Number
Time Frame:Up to 1 year; Pre-dose and multiple time points post-dose after the intravenous infusion
Safety Issue:
Description:
Measure:Terminal Disposition Phase Half-Life (T1/2) Evaluated by CAR Copy Number
Time Frame:Up to 1 year; Pre-dose and multiple time points (Day 1,2,3,4,5,6,7,9,11,14,17,21.28, Month 2 to 6 and Month 7-12)post-dose after the intravenous infusion
Safety Issue:
Description:
Measure:Last Observed Quantifiable Concentration in Peripheral Blood (Clast) Evaluated by CAR Copy Number
Time Frame:Up to 1 year; Pre-dose and multiple time points (Day 1,2,3,4,5,6,7,9,11,14,17,21.28, Month 2 to 6 and Month 7-12) post-dose after the intravenous infusion
Safety Issue:
Description:
Measure:Time of Last Observed Quantifiable Concentration in Peripheral Blood (Tlast) Evaluated by CAR Copy Number
Time Frame:Up to 1 year; Pre-dose and multiple time points (Day 1,2,3,4,5,6,7,9,11,14,17,21.28, Month 2 to 6 and Month 7-12) post-dose after the intravenous infusion
Safety Issue:
Description:
Measure:Area Under the Plasma Concentration-Time Curves (AUCs) Evaluated by CAR Copy Number
Time Frame:Up to 1 year; Pre-dose and multiple time points (Day 1,2,3,4,5,6,7,9,11,14,17,21.28, Month 2 to 6 and Month 7-12) post-dose after the intravenous infusion
Safety Issue:
Description:
Measure:Number of Cases with Replication Competent Retrovirus (RCR)-Positive Test Results
Time Frame:Up to 1 year
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Takeda

Last Updated

August 17, 2020