A Study of TAK-103 in Adult with Solid Tumors
- Conditions
- Solid Tumors
- Interventions
- Biological: TAK-103
- Registration Number
- NCT05164666
- Lead Sponsor
- Takeda
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 2
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description TAK-103, Dose Escalation TAK-103 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Adverse Events of Clinical Interest Up to 1 years 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).
Percentage of Participants with Dose-Limiting Toxicities (DLTs) Up to 28 days 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.
Percentage of Participants With Treatment-emergent Adverse Event (TEAE) Up to 1 years 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.
- Secondary Outcome Measures
Name Time Method Overall response rate (ORR) Assessed by Investigator with RECIST 1.1 Up to 3 years ORR is defined as the percentage of participants whose best overall response is complete response (CR/iCR) or partial response (PR/iPR) as determined by the investigator per RECIST 1.1 and iRECIST respectively. Disease response criteria on RECIST 1.1 are following; Complete response (CR): Disappearance of all target lesions. Partial response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
DCR Assessed by Investigator with iRECIST Up to 3 years DCR is defined as the proportion of patients whose best overall response is stable disease (SD/iSD) or better as determined by the investigator per RECIST 1.1 and iRECIST respectively. SD/iSD have to be maintained for at least 24 days (around 4 weeks) after the TAK-103 infusion.
ORR Assessed by Investigator with immune RECIST (iRECIST) Up to 3 years ORR is defined as the percentage of participants whose best overall response is complete response (CR/iCR) or partial response (PR/iPR) as determined by the investigator per RECIST 1.1 and iRECIST respectively. Disease response criteria on iRECIST are following; Complete Response (iCR), which describes the complete disappearance of target lesion (TL) and Non-TL. All lymph nodes must be non-pathological in size (\< 10 mm in short axis diameter \[SAD\]). Partial Response (iPR), which occurs when the 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. Stable Disease (iSD), which is to be determined if the criteria of iCR or iPR are not met and no tumor progression is present.
Time to Progression (TTP) Assessed by Investigator with RECIST 1.1 Up to 3 years TTP is defined as the time from the TAK-103 infusion date to the date of first documented disease progression by the investigator per RECIST 1.1 and iRECIST respectively.
TTP Assessed by Investigator with iRECIST Up to 3 years TTP is defined as the time from the TAK-103 infusion date to the date of first documented disease progression by the investigator per RECIST 1.1 and iRECIST respectively.
Disease Control Rate (DCR) Assessed by Investigator with RECIST 1.1 Up to 3 years DCR is defined as the proportion of patients whose best overall response is stable disease (SD/iSD) or better as determined by the investigator per RECIST 1.1 and iRECIST respectively. SD/iSD have to be maintained for at least 24 days (around 4 weeks) after the TAK-103 infusion.
DOR Assessed by Investigator with iRECIST Up to 3 years DOR is defined as the time from the date of first documentation of a PR/iPR or better to the date of first documentation of disease progression per RECIST 1.1 and iRECIST respectively.
Progression-Free Survival (PFS) Assessed by Investigator with RECIST 1.1 Up to 3 years PFS is defined as the time from the TAK-103 infusion date to the date of disease progression per RECIST 1.1 and iRECIST respectively or death from any cause, whichever occurs first.
Cmax: Maximum Observed in Peripheral Blood Drug Concentration after Single Dose Administration by CAR Copy Number 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 Clast: Last Observed Quantifiable Concentration in Peripheral Blood by CAR Copy Number 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 Tlast: Persistence: Time of Last Observed Quantifiable Concentration in Peripheral Blood (days) by CAR Copy Number 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 Duration of Response (DOR) Assessed by Investigator with RECIST 1.1 Up to 3 years DOR is defined as the time from the date of first documentation of a PR/iPR or better to the date of first documentation of disease progression per RECIST 1.1 and iRECIST respectively.
PFS Assessed by Investigator with iRECIST Up to 3 years PFS is defined as the time from the TAK-103 infusion date to the date of disease progression per RECIST 1.1 and iRECIST respectively or death from any cause, whichever occurs first.
Overall survival (OS) Up to 3 years OS is defined as the time from the TAK-103 infusion date to the date of death from any cause.
Tmax : Time of First Occurrence of Maximum Observed Peripheral Blood Concentration by CAR Copy Number 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 AUC: Area Under the Blood Concentration-Time Curve by CAR Copy Number 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 Number of Participants with Replication Competent Retrovirus (RCR)-Positive Test Results Up to 3 years
Trial Locations
- Locations (3)
Hyogo College of Medicine Hospital
🇯🇵Nishinomiya, Hyogo, Japan
National Cancer Center Hospital
🇯🇵Chuo-ku, Tokyo, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa, Chiba, Japan