A Study of TAK-103 in Adult With Solid Tumors

NCT05164666 | Terminated Phase 1

• 2 other identifiers: TAK-103-1001jRCT2033210463
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 3

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.

Conditions

Solid Tumors

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants with Dose-Limiting Toxicities (DLTs)

  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.

  Up to 28 days

• Percentage of Participants With Treatment-emergent Adverse Event (TEAE)

  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.

  Up to 1 years

• Percentage of Participants With Adverse Events of Clinical Interest

  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), and tumor lysis syndrome (TLS).

  Up to 1 years

Secondary Outcomes (17)

• Overall response rate (ORR) Assessed by Investigator with RECIST 1.1

  Up to 3 years

• ORR Assessed by Investigator with immune RECIST (iRECIST)

  Up to 3 years

• Disease Control Rate (DCR) Assessed by Investigator with RECIST 1.1

  Up to 3 years

• DCR Assessed by Investigator with iRECIST

  Up to 3 years

• Duration of Response (DOR) Assessed by Investigator with RECIST 1.1

  Up to 3 years

Study Arms (1)

TAK-103, Dose Escalation

EXPERIMENTAL

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.

Biological: TAK-103

Interventions

TAK-103 BIOLOGICAL

TAK-103 intravenous infusion

TAK-103, Dose Escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• Life expectancy \>=12 weeks.
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• Adequate organ function as confirmed by clinical laboratory values as specified below:
• 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
• 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.
• Calculated creatinine clearance \>50 mL/min (Cockcroft-Gault formula).
• Hemoglobin must be \>=9 g/dL.
• Neutrophil count must be \>1000/mm\^3.
• Absolute lymphocyte count must be \>500/mm\^3.
• Platelet count must be \>75,000/mm\^3.
• Participants must have radiographically measurable disease as defined by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1).

You may not qualify if:

• Active systemic infections.
• 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.
• Coagulation disorders, or other major medical illnesses including respiratory or immune system disease.
• 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.
• Participants with current or history of interstitial lung disease.
• 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.
• Participants with any signs of lymphoma and/or leukemia.
• 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.
• Any disease requiring systemic steroid treatment.
• Any prior use of cell and gene therapy(ies).
• 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.
• Systemic anticancer therapy (including immuno-oncology therapies) and treatment with radiotherapy within 14 days before leukapheresis procedures or treatment with conditioning chemotherapy/TAK-103.
• Previous treatment with any mesothelin-targeted therapy.
• Any unresolved toxicity of Grade 3 or higher from previous anticancer therapy.
• Participants with risk of bleeding as judged by the investigator.

Sponsors & Collaborators

• Takeda: lead

Study Sites (3)

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

Location

Hyogo College of Medicine Hospital

Nishinomiya, Hyōgo, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, Japan

Location

Related Links

• To obtain more information on the study, click here/on this link.

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2021
• First Posted: December 21, 2021
• Study Start: January 5, 2022
• Primary Completion: February 22, 2025
• Study Completion: February 22, 2025
• Last Updated: May 29, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

JP (3)