Solid Tumors
Conditions
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.
Interventions
BIOLOGICALTAK-103
TAK-103 intravenous infusion
Sponsors
Takeda
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Dose-Limiting Toxicities (DLTs) | Up to 28 days | DLTs were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Any Grade 3 or higher toxicities that were considered by the investigator to be at least possibly related to therapy with TAK-103 during the 28 days immediately after infusion of TAK-103 and, any adverse events (AEs) requiring endotracheal intubation or tracheostomy were considered as DLTs. |
| Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | From first dose of study drug administration up to 24 months | An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug. An AE can be any unfavourable and unintended sign (including physical examinations, vital signs, electrocardiogram (ECG), laboratory assessment findings), symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug. TEAEs were defined as AEs that newly occurred or worsened on or after the start of study product administration. |
| Percentage of Participants With Adverse Events of Clinical Interest (AECIs) | From first dose of study drug administration up to 24 months | In this study, immune effector cell-associated neurotoxicity syndrome (ICANS), cytokine release syndrome (CRS), hemophagocytic lymphohistiocytosis (HLH), macrophage activation syndrome (MAS), and tumor lysis syndrome (TLS) were predefined as AECIs. CRS and ICANS were evaluated according to American Society for Transplantation and Cellular Therapy (ASTCT) consensus. For management of HLH and MAS, CARTOX (CAR-T-cell-therapy-associated TOXicity) recommendations were used. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) Assessed by Investigator According to RECIST 1.1 | Up to 24 months | ORR was defined as the percentage of participants whose best overall response was complete response (CR) or partial response (PR) as determined by the investigator per Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. Complete Response (CR): Disappearance of all target lesions (TL) and non-target lesions and normalization of tumor marker level. Partial response (PR): At least a 30 percent (%) decrease in the sum of the longest diameter (LD) of TL, taking as reference the baseline sum LD. |
| ORR Assessed by Investigator According to Immune RECIST (iRECIST) | Up to 24 months | ORR was defined as the percentage of participants whose best overall response was immune complete response (iCR) or immune partial response (iPR) as determined by the investigator per iRECIST. Immune Complete Response (iCR): Disappearance of all TL and Non-TL. All lymph nodes must be non-pathological in size (less than \[\<\]10 millimeters \[mm\] in short axis diameter \[SAD\]). Immune Partial Response (iPR): Tumor load of the TL is reduced by less than or equal to (=\<) 30% compared to the baseline, or in the case of complete remission of the TL, when one or more, non-TL can still be distinguished. Immune Stable Disease (iSD), which is to be determined if the criteria of iCR or iPR are not met and no tumor progression is present. |
| Disease Control Rate (DCR) Assessed by Investigator According to RECIST 1.1 | Up to 24 months | DCR was defined as the percentage of participants whose best overall response was CR, PR and stable disease (SD) or better as determined by the investigator per RECIST version 1.1. CR: Disappearance of all TL and Non-TL. All lymph nodes must be non-pathological in size (\< 10 mm in SAD). PR: Tumor load of the TL is reduced by =\<30% compared to the baseline, or in the case of complete remission of the TL, when one or more, Non-TL can still be distinguished.SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD), taking as reference the smallest sum LD since the treatment started. SD have to be maintained for at least 24 days (around 4 weeks) after the TAK-103 infusion. |
| DCR Assessed by Investigator According to iRECIST | Up to 24 months | DCR was defined as the percentage of participants whose best overall response was iCR, iPR and iSD or better as determined by the investigator per iRECIST. iCR: Disappearance of all TL and Non-TL. All lymph nodes must be non-pathological in size (\< 10 mm in SAD). iPR: Tumor load of the TL is reduced by =\<30% compared to the baseline, or in the case of complete remission of the TL, when one or more, non-TL can still be distinguished. iSD: Determined if the criteria of iCR or iPR are not met and no tumor progression is present. |
| Duration of Response (DOR) Assessed by Investigator With RECIST 1.1 | Up to 24 months | DOR was defined as the time from the date of first documentation of a PR or better to the date of first documentation of PD per RECIST version 1.1. 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 diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). |
| DOR Assessed by Investigator With iRECIST | Up to 24 months | DOR was defined as the time from the date of first documentation of an iPR or better to the date of first documentation of disease progression per iRECIST. iPR: Tumor load of the TL is reduced by =\<30% compared to the baseline, or in the case of complete remission of the TL, when one or more, non-TL can still be distinguished. |
| Time to Progression (TTP) Assessed by Investigator With RECIST 1.1 | Up to 24 months | TTP was defined as the time from the TAK-103 infusion date to the date of first documented disease progression by the investigator per RECIST version 1.1. |
| TTP Assessed by Investigator With iRECIST | Up to 24 months | TTP was defined as the time from the TAK-103 infusion date to the date of first documented disease progression by the investigator per iRECIST. |
| Progression-Free Survival (PFS) Assessed by Investigator With RECIST 1.1 | Up to 24 months | PFS was defined as the time from the TAK-103 infusion date to the date of disease progression per RECIST version 1.1 or death from any cause, whichever occurred first. |
| PFS Assessed by Investigator With iRECIST | Up to 24 months | PFS was defined as the time from the TAK-103 infusion date to the date of disease progression per iRECIST or death from any cause, whichever occurred first. |
| Overall Survival (OS) | Up to 24 months | OS was defined as the time from the TAK-103 infusion date to the date of death from any cause. Participants who did not die were censored at the last known survival follow-up. |
| Cmax- Maximum Observed in Peripheral Blood Drug Concentration After Single Dose Administration by CAR Copy Number of TAK-103 | At 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 | — |
| Tmax- Time of First Occurrence of Maximum Observed Peripheral Blood Concentration by CAR Copy Number of TAK-103 | At 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 | — |
| Clast- Last Observed Quantifiable Concentration in Peripheral Blood by CAR Copy Number of TAK-103 | At Pre-dose and multiple time points (Day 1, 2, 4, 8, 11, 15, 18 and 22) post-dose | — |
| Tlast- Persistence: Time of Last Observed Quantifiable Concentration in Peripheral Blood (Days) by CAR Copy Number of TAK-103 | At Pre-dose and multiple time points (Day 1, 2, 4, 8, 11, 15, 18 and 22) post-dose | — |
| AUC- Area Under the Blood Concentration-Time Curve by CAR Copy Number of TAK-103 | At Pre-dose and multiple time points (Day 1, 2, 4, 8, 11, 15, 18, 22, and 29) post-dose | — |
| Number of Participants With Replication Competent Retrovirus (RCR)-Positive Test Results | Up to 24 months | Number of participants with RCR-Positive test results were reported. |
Countries
Japan
Contacts
STUDY_DIRECTORStudy Director
Takeda
Participant flow
Recruitment details
Participants took part in the study at 2 investigative sites in Japan from 05 January 2022 to 22 February 2025.
Pre-assignment details
A total of 20 participants were screened, of which 18 participants were screen failures and the remaining 2 were enrolled in the study. The study was terminated early by the sponsor due to a business decision unrelated to patient safety.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 1 | 1 / 1 |
| other Total, other adverse events | 1 / 1 | 1 / 1 |
| serious Total, serious adverse events | 1 / 1 | 1 / 1 |
Outcome results
None listed