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.
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.
