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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04405778
Recruitment Status : Not yet recruiting
First Posted : May 28, 2020
Last Update Posted : June 2, 2020
Sponsor:
Information provided by (Responsible Party):
Takeda

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Solid Tumors Biological: TAK-102 Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : June 19, 2020
Estimated Primary Completion Date : November 11, 2022
Estimated Study Completion Date : November 11, 2022

Arm Intervention/treatment
Experimental: TAK-102 Cohort 1
TAK-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.
Biological: TAK-102
TAK-102 intravenous infusion

Experimental: TAK-102 Cohort 2
TAK-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.
Biological: TAK-102
TAK-102 intravenous infusion

Experimental: TAK-102 Cohort 3
TAK-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.
Biological: TAK-102
TAK-102 intravenous infusion




Primary Outcome Measures :
  1. Number of Participants with First Cycle Dose-Limiting Toxicities (DLTs) [ Time Frame: Up to 28 days ]
    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.

  2. Number of Participants With One or More Treatment-emergent Adverse Event (TEAE) [ Time Frame: Up to 1 year ]
    An adverse event (AE) means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This includes any newly occurring event, or a previous condition that has increased in severity or frequency since the administration of study drug.

  3. Number of Participants With Adverse Events of Clinical Interest [ Time Frame: Up to 1 year ]
    Adverse events of clinical interest include severe immune effector cell-associated neurotoxicity syndrome (ICANS), cytokine release syndrome (CRS), hemophagocytic lymphohistiocytosis (HLH), macrophage activation syndrome (MAS), tumor lysis syndrome (TLS), and liver function abnormality.


Secondary Outcome Measures :
  1. 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 ]
    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.

  2. Duration of Response (DOR) as Assessed by the Investigator [ Time Frame: Up to 1 year ]
    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.

  3. Disease Control Rate (DCR) as Assessed by the Investigator [ Time Frame: Up to 1 year ]
    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.

  4. Time to Progression as Assessed by the Investigator [ Time Frame: Up to 1 year ]
    TTP is defined as the time from the date of study drug administration to the date of first documented disease progression by the investigator.

  5. Progression-Free Survival (PFS) as Assessed by the Investigator [ Time Frame: Up to 1 year ]
    PFS is defined as the time from the TAK-102 infusion date to the date of disease progression or death from any cause.

  6. Overall Survival (OS) [ Time Frame: Up to 1 year ]
    OS is defined as the time from the TAK-102 infusion to the date of death from any cause.

  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
  11. 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 ]
  12. 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 ]
  13. Number of Cases with Replication Competent Retrovirus (RCR)-Positive Test Results [ Time Frame: Up to 1 year ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04405778


Contacts
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Contact: Takeda Study Registration Call Center +1-866-835-2233 globaloncologymedinfo@takeda.com

Sponsors and Collaborators
Takeda
Investigators
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Study Director: Study Director Takeda
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Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT04405778    
Other Study ID Numbers: TAK-102-1501
U1111-1247-6429 ( Other Identifier: WHO )
First Posted: May 28, 2020    Key Record Dates
Last Update Posted: June 2, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms