Clinical trial NCT05164666: A Study of TAK-103 in Adult With Solid Tumors
Official title: An Open-Label, Dose Escalation, Phase 1, First-in-Human Study of TAK-103 in Adult Patients With Mesothelin-Expressing Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Solid Tumors
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2021-12-21
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In this study, people with mesothelin-expressing advanced or metastatic solid tumors will receive TAK-103 with their white blood cells. The main aims of this study are to check if the participants get any side effects from treatment with TAK-103 and to check how much TAK-103 participants can receive without getting side effects from it. Researchers can then work out the best dose of TAK-103 to give to participants in future studies.

At the first visit, the study doctor will check who can take part. For those who can take part, the study doctors will collect white blood cells from each participant. These cells are sent to the laboratory where TAK-103 is added to each participant's cells. This can take up to 4 or 5 weeks. Participants may receive specific treatments while participants are waiting for TAK-103. Then, participants will receive TAK-103 with their cells slowly through a vein (infusion). Participants will receive lower to higher doses of TAK-103. Each participant will just receive 1 dose. The study doctors will check for side effects after each different dose of TAK-103. In this way, researchers can work out the best dose of TAK-103 to give to participants in future studies.

Participants will stay in hospital for 28 days or longer for their treatment. Then, participants will visit the clinic for regular check-ups for up to 3 years.


Eligibility criteria: Inclusion Criteria

1. Histologically or cytologically confirmed advanced or metastatic solid tumors who have no option with or are intolerant of standard therapies with a proven clinical benefit.
2. Mesothelin-expression (\>=50% positive on viable tumor cells) must be determined on the tumor by immunohistochemistry using a validated assay, scoring and staining confirmed by the sponsor prior to leukapheresis procedures.
3. Life expectancy \>=12 weeks.
4. Eastern Cooperative Oncology Group performance status of 0 or 1.
5. Adequate organ function as confirmed by clinical laboratory values as specified below:

   1. Total bilirubin =\<1.5 × the upper limit of the normal range (ULN) except in Participants with Gilbert's syndrome. Participants with Gilbert's syndrome may enroll with direct bilirubin =\<3 × ULN of the direct bilirubin. Elevated indirect bilirubin due to posttransfusion hemolysis is allowed
   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 the liver.
   3. Calculated creatinine clearance \>50 mL/min (Cockcroft-Gault formula).
   4. Hemoglobin must be \>=9 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.
6. Participants must have radiographically measurable disease as defined by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1).

Exclusion Criteria

1. Active systemic infections.
2. Known hepatitis B surface antigen (HBsAg) positive, or known or suspected active hepatitis C virus (HCV) infection. Participants who have positive hepatitis B core antibody (HBcAb) or hepatitis B surface antibody (HBsAb) can be enrolled but must have an undetectable hepatitis B virus (HBV) viral load. Participants who have positive hepatitis C virus antibody (HCVAb) must have an undetectable HCV viral load.
3. Coagulation disorders, or other major medical illnesses including respiratory or immune system disease.
4. Participants with high tumor burden at the disease assessment at screening. The tumor burden is determined by the threshold set for each type of cancer.
5. Participants with current or history of interstitial lung disease.
6. Participants with current or history of significant immune-related adverse events (irAEs) related to treatment with immune checkpoint inhibitors. Patients with current or history of the following adverse events (AEs) can be enrolled after careful discussion between the investigator and sponsor: hyperglycemia/diabetes mellitus, thyroid disorder, hypopituitarism, hypoadrenocorticism, asymptomatic elevation in amylase/lipase, and Grade1 or 2 skin toxicity.
7. Participants with known cardiovascular and cardiopulmonary disease defined as unstable angina, clinically significant arrhythmia, myocardial infarction, congestive heart failure, left ventricular ejection fraction (LVEF) \<45 %, impaired respiratory function, baseline oxygen saturation \<93% on room air. A well-controlled atrial fibrillation would not be an exclusion whereas uncontrolled atrial fibrillation would be an exclusion.
8. Participants with any signs of lymphoma and/or leukemia.
9. Participants who are diagnosed with or treated for another malignancy within 3 years before leukapheresis procedures. Participants with non-melanoma skin cancer or carcinoma in situ (eg, cervix, bladder, breast) would be included if they were adequately treated.
10. Any disease requiring systemic steroid treatment.
11. Any prior use of cell and gene therapy(ies).
12. Treatment with any investigational products (except for cell or gene therapy) within 14 days before leukapheresis procedures or 28 days before treatment with conditioning chemotherapy/TAK-103.
13. Systemic anticancer therapy (including immuno-oncology therapies) and treatment with radiotherapy within 14 days before leukapheresis procedures or treatment with conditioning chemotherapy/TAK-103.
14. Treatment with major surgery within 28 days before leukapheresis procedures or treatment with conditioning chemotherapy/TAK-103 (minor surgical procedures such as catheter placement are not exclusionary criteria).
15. Previous treatment with any mesothelin-targeted therapy.
16. Any unresolved toxicity of Grade 3 or higher from previous anticancer therapy.
17. Participants with risk of bleeding as judged by the investigator.
18. Presence of central nervous system metastasis or other significant neurological conditions (Participant with central nervous system metastases that have been effectively treated where necessary and stable can be enrolled).
19. Participants with human immunodeficiency virus (HIV) seropositive and/or human T-cell lymphotropic virus (HTLV) seropositive.
20. Participants with a history of organ transplantation or awaiting organ transplantation.
21. Participants with severe immediate hypersensitivity to any of the agents including cyclophosphamide, fludarabine, or streptomycin.

Primary outcomes:
measure: Percentage of Participants with Dose-Limiting Toxicities (DLTs)
timeFrame: Up to 28 days
measure: Percentage of Participants With Treatment-emergent Adverse Event (TEAE)
timeFrame: Up to 1 years
measure: Percentage of Participants With Adverse Events of Clinical Interest
timeFrame: Up to 1 years
Secondary outcomes:
measure: Overall response rate (ORR) Assessed by Investigator with RECIST 1.1
timeFrame: Up to 3 years
measure: ORR Assessed by Investigator with immune RECIST (iRECIST)
timeFrame: Up to 3 years
measure: Disease Control Rate (DCR) Assessed by Investigator with RECIST 1.1
timeFrame: Up to 3 years
measure: DCR Assessed by Investigator with iRECIST
timeFrame: Up to 3 years
measure: Duration of Response (DOR) Assessed by Investigator with RECIST 1.1
timeFrame: Up to 3 years
measure: DOR Assessed by Investigator with iRECIST
timeFrame: Up to 3 years
measure: Time to Progression (TTP) Assessed by Investigator with RECIST 1.1
timeFrame: Up to 3 years
measure: TTP Assessed by Investigator with iRECIST
timeFrame: Up to 3 years
measure: Progression-Free Survival (PFS) Assessed by Investigator with RECIST 1.1
timeFrame: Up to 3 years
measure: PFS Assessed by Investigator with iRECIST
timeFrame: Up to 3 years
measure: Overall survival (OS)
timeFrame: Up to 3 years
measure: Cmax: Maximum Observed in Peripheral Blood Drug Concentration after Single Dose Administration by CAR Copy Number
timeFrame: Up to 13 months; Pre-dose and multiple time points (Day 1, 2, 4, 8, 11, 15, 18, 22, 29, Months 3, 4, 5, 7, 10, and 13) post-dose after the intravenous infusion
measure: Tmax : Time of First Occurrence of Maximum Observed Peripheral Blood Concentration by CAR Copy Number
timeFrame: Up to 13 months; Pre-dose and multiple time points (Day 1, 2, 4, 8, 11, 15, 18, 22, 29, Months 3, 4, 5, 7, 10, and 13) post-dose after the intravenous infusion
measure: Clast: Last Observed Quantifiable Concentration in Peripheral Blood by CAR Copy Number
timeFrame: Up to 13 months; Pre-dose and multiple time points (Day 1, 2, 4, 8, 11, 15, 18, 22, 29, Months 3, 4, 5, 7, 10, and 13) post-dose after the intravenous infusion
measure: Tlast: Persistence: Time of Last Observed Quantifiable Concentration in Peripheral Blood (days) by CAR Copy Number
timeFrame: Up to 13 months; Pre-dose and multiple time points (Day 1, 2, 4, 8, 11, 15, 18, 22, 29, Months 3, 4, 5, 7, 10, and 13) post-dose after the intravenous infusion
measure: AUC: Area Under the Blood Concentration-Time Curve by CAR Copy Number
timeFrame: Up to 13 months; Pre-dose and multiple time points (Day 1, 2, 4, 8, 11, 15, 18, 22, 29, Months 3, 4, 5, 7, 10, and 13) post-dose after the intravenous infusion
measure: Number of Participants with Replication Competent Retrovirus (RCR)-Positive Test Results
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Nishinomiya
country: Japan
facility: Hyogo College of Medicine Hospital
state: Hyogo
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: