A Study of TAK-103 in Adult with Solid Tumors

Takeda

Status and phase: Active, not recruiting; Phase 1

Conditions: Solid Tumors

Treatments: Biological: TAK-103

Study type: Interventional

Funder types: Industry

Identifiers

NCT05164666

jRCT2033210463 (Registry Identifier)

TAK-103-1001

Details and patient eligibility

About

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.

Enrollment: 2 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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2 participants in 1 patient group

TAK-103, Dose Escalation

Experimental group

Description:

TAK-103, Chimeric antigen receptor (CAR) (+) cells, intravenous infusion, will be administered at approximately 5 mL/min. There are 5 planned dose levels: 1x10\^6, 3x10\^6, 1x10\^7, 1x10\^8 and 5x10\^8 CAR (+) cells/body. The level of dose in dose escalation will be guided by dose escalation schema based on the observed dose limiting toxicities (DLT) rate at each dose level.

Treatment:

Biological: TAK-103