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A Study of TAK-103 in Adult With Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05164666
Recruitment Status : Recruiting
First Posted : December 21, 2021
Last Update Posted : March 11, 2022
Sponsor:
Information provided by (Responsible Party):
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). 4 different small groups of 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.


Condition or disease Intervention/treatment Phase
Solid Tumors Biological: TAK-103 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 21 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 5, 2022
Estimated Primary Completion Date : October 31, 2026
Estimated Study Completion Date : October 31, 2026

Arm Intervention/treatment
Experimental: TAK-103 Cohort 1
TAK-103, 1 × 10^7 Chimeric antigen receptor (CAR) (+) cells/body as a starting dose, intravenous infusion, will be administered at approximately 5 mL/min.
Biological: TAK-103
TAK-103 intravenous infusion

Experimental: TAK-103 Cohort 2
TAK-103, 1 × 10^8 CAR (+) cells/body as a starting dose, intravenous infusion, will be administered at approximately 5 mL/min.
Biological: TAK-103
TAK-103 intravenous infusion

Experimental: TAK-103 Cohort 3
TAK-103, 5 × 10^8 CAR (+) cells/body as a starting dose, intravenous infusion, will be administered at approximately 5 mL/min.
Biological: TAK-103
TAK-103 intravenous infusion

Experimental: TAK-103 Cohort 4
TAK-103, 1 × 10^9 CAR (+) cells/body as a starting dose, intravenous infusion, will be administered at approximately 5 mL/min.
Biological: TAK-103
TAK-103 intravenous infusion




Primary Outcome Measures :
  1. Percentage of Participants with Dose-Limiting Toxicities (DLTs) [ Time Frame: 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.

  2. Percentage of Participants With Treatment-emergent Adverse Event (TEAE) [ Time Frame: 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.

  3. Percentage of Participants With Adverse Events of Clinical Interest [ Time Frame: 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).


Secondary Outcome Measures :
  1. Overall response rate (ORR) Assessed by Investigator with RECIST 1.1 [ Time Frame: 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.

  2. ORR Assessed by Investigator with immune RECIST (iRECIST) [ Time Frame: 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.

  3. Disease Control Rate (DCR) Assessed by Investigator with RECIST 1.1 [ Time Frame: 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.

  4. DCR Assessed by Investigator with iRECIST [ Time Frame: 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.

  5. Duration of Response (DOR) Assessed by Investigator with RECIST 1.1 [ Time Frame: 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.

  6. DOR Assessed by Investigator with iRECIST [ Time Frame: 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.

  7. Time to Progression (TTP) Assessed by Investigator with RECIST 1.1 [ Time Frame: 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.

  8. TTP Assessed by Investigator with iRECIST [ Time Frame: 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.

  9. Progression-Free Survival (PFS) Assessed by Investigator with RECIST 1.1 [ Time Frame: 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.

  10. PFS Assessed by Investigator with iRECIST [ Time Frame: 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.

  11. Overall survival (OS) [ Time Frame: Up to 3 years ]
    OS is defined as the time from the TAK-103 infusion date to the date of death from any cause.

  12. Cmax: Maximum Observed in Peripheral Blood Drug Concentration after Single Dose Administration by CAR Copy Number [ Time Frame: 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 ]
  13. Tmax : Time of First Occurrence of Maximum Observed Peripheral Blood Concentration by CAR Copy Number [ Time Frame: 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 ]
  14. Clast: Last Observed Quantifiable Concentration in Peripheral Blood by CAR Copy Number [ Time Frame: 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 ]
  15. Tlast: Persistence: Time of Last Observed Quantifiable Concentration in Peripheral Blood (days) by CAR Copy Number [ Time Frame: 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 ]
  16. AUC: Area Under the Blood Concentration-Time Curve by CAR Copy Number [ Time Frame: 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 ]
  17. Number of Participants with Replication Competent Retrovirus (RCR)-Positive Test Results [ Time Frame: Up to 3 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 locally by immunohistochemistry using a validated assay, scoring and staining confirmed by the sponsor. Fresh biopsy sample must be used for eligibility assessment unless archived biopsy sample obtained within 6 months prior to leukapheresis procedures is available.
  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 known cardiovascular and cardiopulmonary disease defined as unstable angina, clinically significant arrhythmia, myocardial infarction, congestive heart failure, left ventricular ejection fraction (LVEF) <45 %, 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.
  5. Participants with any signs of lymphoma and/or leukemia.
  6. 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.
  7. Any disease requiring systemic steroid treatment.
  8. Any prior use of cell and gene therapy(ies).
  9. 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.
  10. Systemic anticancer therapy (including immuno-oncology therapies) and treatment with radiotherapy within 14 days before leukapheresis procedures or treatment with conditioning chemotherapy/TAK-103.
  11. 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).
  12. Previous treatment with any mesothelin-targeted therapy.
  13. Any unresolved toxicity of Grade 3 or higher from previous anticancer therapy.
  14. Participants with risk of bleeding as judged by the investigator.
  15. 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).
  16. Participants with human immunodeficiency virus (HIV) seropositive and/or human T-cell lymphotropic virus (HTLV) seropositive.
  17. Participants with a history of organ transplantation or awaiting organ transplantation.
  18. Participants with severe immediate hypersensitivity to any of the agents including cyclophosphamide, fludarabine, or streptomycin.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05164666


Contacts
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Contact: Takeda Contact +1-877-825-3327 medinfoUS@takeda.com

Locations
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Japan
National Cancer Center Hospital East Recruiting
Kashiwa, Chiba, Japan
Hyogo College of Medicine Hospital Not yet recruiting
Nishinomiya, Hyogo, Japan
National Cancer Center Hospital Recruiting
Chuo-ku, Tokyo, Japan
Sponsors and Collaborators
Takeda
Investigators
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Study Director: Study Director Takeda
Additional Information:
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Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT05164666    
Other Study ID Numbers: TAK-103-1001
jRCT2033210463 ( Registry Identifier: jRCT )
First Posted: December 21, 2021    Key Record Dates
Last Update Posted: March 11, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/ For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
URL: https://vivli.org/ourmember/takeda/

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms