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A Basket Study of Customized Autologous TCR-T Cell Therapies in Patients With Locally Advanced (Unresectable) or Metastatic 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: NCT05973487
Recruitment Status : Recruiting
First Posted : August 3, 2023
Last Update Posted : May 10, 2024
Sponsor:
Information provided by (Responsible Party):
TScan Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE July 25, 2023
First Posted Date  ICMJE August 3, 2023
Last Update Posted Date May 10, 2024
Actual Study Start Date  ICMJE May 6, 2024
Estimated Primary Completion Date December 30, 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 1, 2023)
  • Evaluate the safety of monotherapy and T- Plex combination TCR-Ts [ Time Frame: 28 days ]
    Number of subjects with dose limiting toxicities (DLT)
  • Determine the recommended phase 2 dose of monotherapy and T- Plex combination TCR-Ts [ Time Frame: Up to 12 months ]
    Frequency and severity of DLTs, AEs and SAEs
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 1, 2023)
  • Investigate preliminary anti-tumor activity of monotherapy and T- Plex combination TCR-Ts [ Time Frame: Up to 12 months ]
    Response Evaluation Criteria In Solid Tumors RECIST 1.1
  • Investigate the feasibility of repeat dosing of monotherapy and T- Plex combination TCR-Ts [ Time Frame: Up to 12 months ]
    Frequency and severity of DLTs, AEs and SAEs
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: August 1, 2023)
  • To measure the persistence of T-Plex TCR-T cells in the peripheral blood with single and repeat doses [ Time Frame: Up to 24 months ]
    Percentage of TCR-T cells in the peripheral blood after single and repeat doses
  • To measure the infiltration of T-Plex TCR-T cells into tumors in post-treatment biopsies [ Time Frame: Up to 24 months ]
    Percentage of TCR-T cells in the tumor after single and repeat doses
  • To measure the immune activation markers in the tumor after single and repeated doses [ Time Frame: Up to 24 months ]
    Status of immune activation markers in the tumor after single and repeat doses
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE A Basket Study of Customized Autologous TCR-T Cell Therapies in Patients With Locally Advanced (Unresectable) or Metastatic Solid Tumors
Official Title  ICMJE A Phase 1 Basket Study Evaluating the Safety and Feasibility of T-Plex, Autologous Customized T Cell Receptor-Engineered T Cells Targeting Multiple Peptide/HLA Antigens in Participants With Antigen-positive Locally Advanced (Unresectable) or Metastatic Solid Tumors
Brief Summary

TScan Therapeutics is developing cellular therapies across multiple solid tumors in which autologous participant-derived T cells are engineered to express a T cell receptor that recognizes cancer-associated antigens presented on specific Human Leukocyte Antigen (HLA) molecules.

This is a multi-center, non-randomized, multi-arm, open-label, basket study evaluating the safety and preliminary efficacy of single and repeat dose regimens of TCR'Ts as monotherapies and as T-Plex combinations after lymphodepleting chemotherapy in participants with locally advanced, metastatic solid tumors disease.
Detailed Description

Participants will be screened in a separate screening study, TSCAN-003 (NCT05812027), to assess their HLA type, tumor-associated antigen (TAA) expression and loss of heterozygosity (LOH) status. The results of these tests will be used to determine initial eligibility in this study.

Depending on the genetic type, participants will be assigned to one of the following study groups:

Monotherapy:

  • COHORT A: TSC-204-A0201 targeting MAGE-A1 on HLA-A*02:01
  • COHORT B: TSC-204-C0702 targeting MAGE-A1 on HLA-C*07:02
  • COHORT C: TSC-200-A0201 targeting HPV16 E7 on HLA-A*02:01
  • COHORT D: TSC-203-A0201 targeting PRAME on HLA-A*02:01
  • COHORT E: TSC-204-A0101 targeting MAGE-A1 on HLA-A*01:01
  • COHORT F: TSC-201-B0702 targeting MAGE-C2 on HLA-B*07:02

T-Plex Combination:

  • COHORT AB: TSC-204-A0201 + TSC-204-C0702
  • COHORT AC: TSC-204-A0201 + TSC-200-A0201
  • COHORT AD: TSC-204-A0201 + TSC-203-A0201
  • COHORT AE: TSC-204-A0201 + TSC-204-A0101
  • COHORT AF: TSC-204-A0201 + TSC-201-B0702
  • COHORT BC: TSC-204-C0702 + TSC-200-A0201
  • COHORT BD: TSC-204-C0702 + TSC-203-A0201
  • COHORT BE: TSC-204-C0702 + TSC-204-A0101
  • COHORT BF: TSC-204-C0702 + TSC-201-B0702
  • COHORT CD: TSC-200-A0201 + TSC-203-A0201
  • COHORT CE: TSC-200-A0201 + TSC-204-A0101
  • COHORT CF: TSC-200-A0201 + TSC-201-B0702
  • COHORT DE: TSC-203-A0201 + TSC-204-A0101
  • COHORT DF: TSC-203-A0201 + TSC-201-B0702
  • COHORT EF: TSC-204-A0101 + TSC-201-B0702

Participants will undergo leukapheresis to collect cells to manufacture the TCR-T products. They will then undergo lymphodepletion and receive one or two doses of the TCR-T cell therapy product as a monotherapy or part of a combination of TCR-Ts (referred to as T-Plex combinations in this study).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Head and Neck Cancer
  • Cervical Cancer
  • Non-small Cell Carcinoma
  • Melanoma
  • Ovarian Cancer
  • Anogenital Cancers
  • HPV - Anogenital Human Papilloma Virus Infection
  • HPV-Related Cervical Carcinoma
  • HPV-Related Carcinoma
  • HPV-Related Squamous Cell Carcinoma
  • HPV-Related Malignancy
  • HPV-Related Adenocarcinoma
  • HPV Positive Oropharyngeal Squamous Cell Carcinoma
  • HPV-Related Adenosquamous Carcinoma
  • HPV-Associated Vaginal Adenocarcinoma
  • HPV-Related Endocervical Adenocarcinoma
  • HPV-Related Anal Squamous Cell Carcinoma
  • HPV-Related Verrucous Carcinoma
  • HPV-Related Penile Squamous Cell Carcinoma
  • HPV-Related Vulvar Squamous Cell Carcinoma
  • HPV Positive Rectal Squamous Cell Carcinoma
Intervention  ICMJE
  • Biological: TSC-204-A0201
    Escalating doses of TSC-204-A0201 as a monotherapy
  • Biological: TSC-204-C0702
    Escalating doses of TSC-204-C0702 as a monotherapy
  • Biological: TSC-200-A0201
    Escalating doses of TSC-200-A0201 as a monotherapy
  • Biological: TSC-204-A0201 + TSC-204-C0702
    Escalating doses of TSC-204-A0201 in combination with TSC-204-C0702
  • Biological: TSC-204-A0201 + TSC-200-A0201
    Escalating doses of TSC-204-A0201 in combination with TSC-200-A0201
  • Biological: TSC-204-C0702 + TSC-200-A0201
    Escalating doses of TSC-204-C0702 in combination with TSC-200-A0201
  • Biological: TSC-204-A0201 + TSC-203-A0201
    Escalating doses of TSC-204-A0201 in combination with TSC-203-A0201
  • Biological: TSC-204-C0702 + TSC-203-A0201
    Escalating doses of TSC-204-C0702 in combination with TSC-203-A0201
  • Biological: TSC-200-A0201 + TSC-203-A0201
    Escalating doses of TSC-200-A0201 in combination with TSC-203-A0201
  • Biological: TSC-203-A0201
    Escalating doses of TSC-203-A0201 as a monotherapy
  • Biological: TSC-204-A0101
    Escalating doses of TSC-204-A0101 as a monotherapy
  • Biological: TSC-201-B0702
    Escalating doses of TSC-201-B0702 as a monotherapy
  • Biological: TSC-204-A0201 + TSC-204-A0101
    Escalating doses of TSC-204-A0201 in combination with TSC-204-A0101
  • Biological: TSC-204-A0201 + TSC-201-B0702
    Escalating doses of TSC-204-A0201 in combination with TSC-201-B0702
  • Biological: TSC-204-C0702 + TSC-204-A0101
    Escalating doses of TSC-204-C0702 in combination with TSC-204-A0101
  • Biological: TSC-204-C0702 + TSC-201-B0702
    Escalating doses of TSC-204-C0702 in combination with TSC-201-B0702
  • Biological: TSC-200-A0201 + TSC-204-A0101
    Escalating doses of TSC-200-A0201 in combination with TSC-204-A0101
  • Biological: TSC-200-A0201 + TSC-201-B0702
    Escalating doses of TSC-200-A0201 in combination with TSC-201-B0702
  • Biological: TSC-203-A0201 + TSC-204-A0101
    Escalating doses of TSC-203-A0201 in combination with TSC-204-A0101
  • Biological: TSC-203-A0201 + TSC-201-B0702
    Escalating doses of TSC-203-A0201 in combination with TSC-201-B0702
Study Arms  ICMJE
  • Experimental: Monotherapy Cohort A
    TSC-204-A0201
    Intervention: Biological: TSC-204-A0201
  • Experimental: Monotherapy Cohort B
    TSC-204-C0702
    Intervention: Biological: TSC-204-C0702
  • Experimental: Monotherapy Cohort C
    TSC-200-A0201
    Intervention: Biological: TSC-200-A0201
  • Experimental: T-Plex Combination Cohort A + B
    TSC-204-A0201 and TSC-204-C0702
    Intervention: Biological: TSC-204-A0201 + TSC-204-C0702
  • Experimental: T-Plex Combination Cohort B + C
    TSC-204-C0702 and TSC-200-A0201
    Intervention: Biological: TSC-204-A0201 + TSC-200-A0201
  • Experimental: T-Plex Combination Cohort A + C
    TSC-204-A0201 and TSC-200-A0201
    Intervention: Biological: TSC-204-C0702 + TSC-200-A0201
  • Experimental: Monotherapy Cohort D
    TSC-203-A0201
    Intervention: Biological: TSC-203-A0201
  • Experimental: T-Plex Combination Cohort A + D
    TSC-204-A0201 + TSC-203-A0201
    Intervention: Biological: TSC-204-A0201 + TSC-203-A0201
  • Experimental: T-Plex Combination Cohort B + D
    TSC-204-C0702 + TSC-203-A0201
    Intervention: Biological: TSC-204-C0702 + TSC-203-A0201
  • Experimental: Monotherapy Cohort E
    TSC-204-A0101
    Intervention: Biological: TSC-204-A0101
  • Experimental: Monotherapy Cohort F
    TSC-201-B0702
    Intervention: Biological: TSC-201-B0702
  • Experimental: T-Plex Combination Cohort A + E
    TSC-204-A0201 + TSC-204-A0101
    Intervention: Biological: TSC-204-A0201 + TSC-204-A0101
  • Experimental: T-Plex Combination Cohort A + F
    TSC-204-A0201 + TSC-201-B0702
    Intervention: Biological: TSC-204-A0201 + TSC-201-B0702
  • Experimental: T-Plex Combination Cohort B + E
    TSC-204-C0702 + TSC-204-A0101
    Intervention: Biological: TSC-204-C0702 + TSC-204-A0101
  • Experimental: T-Plex Combination Cohort B + F
    TSC-204-C0702 + TSC-201B0702
    Intervention: Biological: TSC-204-C0702 + TSC-201-B0702
  • Experimental: T-Plex Combination Cohort C + D
    TSC-200-A0201 + TSC-203-A0201
    Intervention: Biological: TSC-200-A0201 + TSC-203-A0201
  • Experimental: T-Plex Combination Cohort C + E
    TSC-200-A0201 + TSC-204-A0101
    Intervention: Biological: TSC-200-A0201 + TSC-204-A0101
  • Experimental: T-Plex Combination Cohort C + F
    TSC-200-A0201 + TSC-201B0702
    Intervention: Biological: TSC-200-A0201 + TSC-201-B0702
  • Experimental: T-Plex Combination Cohort D + E
    TSC-203-A0201 + TSC-204A0101
    Intervention: Biological: TSC-203-A0201 + TSC-204-A0101
  • Experimental: T-Plex Combination Cohort D + F
    TSC-203-A0201 + TSC-201B0702
    Intervention: Biological: TSC-203-A0201 + TSC-201-B0702
  • Experimental: T-Plex Combination Cohort E + F
    TSC-204-A0101 + TSC-201-B0702
    Interventions:
    • Biological: TSC-204-A0101
    • Biological: TSC-201-B0702
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 1, 2023)		 100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 30, 2026
Estimated Primary Completion Date December 30, 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Must be at least 18 years.
  2. Locally advanced (unresectable) or metastatic solid tumor for which there are no available curative treatment options, after failure of the standard of care systemic therapies for that particular indication.
  3. Solid tumors, including but not limited to non-nasopharyngeal head and neck cancer, non-small cell lung cancer, cutaneous melanoma, cervical cancer, ovarian cancer, anal cancer and genital cancers. Other tumor types may be permitted if approved by TScan.

  4. Participants must express one of the following HLA types, as assessed by a qualified genomics assay in screening study TSCAN-003:

    HLA-B*07:02 HLA-A*01:01 HLA-C*07:02 HLA-A*02:01

  5. Tumor must express one or more of the following: MAGE-A1, MAGE-C2, PRAME and HPV16-E7 assessed in the last 8 months in screening study TSCAN-003 (NCT05812027).
  6. Eastern Cooperative Oncology Group (ECOG) Performance status 0-1 at screening.
  7. Participants must be able to understand and be willing to give informed consent; decision-impaired adults may consent with their legally authorized representative.
  8. At least 1 measurable lesion per modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
  9. Adequate bone marrow and organ function.

Exclusion Criteria:

  1. Medical or psychological conditions that would make the participant unsuitable candidate for cell therapy at the discretion of the PI.
  2. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, cardiac arrhythmia requiring antiarrhythmic or procedure, or other clinically significant cardiac disease within 12 months of enrollment
  3. History of stroke or transient ischemic attack (TIA) within 12 months of enrollment
  4. Systemic corticosteroid therapy >10 mg of prednisone daily or equivalent within 7 days of enrollment
  5. History of severe hypersensitivity to fludarabine or cyclophosphamide or study product excipients including human serum albumin, Cryostor (DMSO or Dextran 40), or Plasma-Lyte.
  6. Untreated or symptomatic central nervous system (CNS) metastases or cytology proven carcinomatous meningitis.
  7. Concurrent receipt of another anti-cancer therapy.
  8. Presence of fungal, bacterial, viral, or other infection requiring anti-microbials for management.
  9. Tumors that have HLA LOH using a central lab clinical trial assay of HLAs addressed by the monotherapy and/or T-Plex combination TCR-Ts in the protocol and have no available TCR-T options for intact HLAs in the participant's tumor.
  10. Participants who regularly require supplemental oxygen.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Marlyane Motta, BS 857-399-9887 mmotta@tscan.com
Contact: OncoBay Clinical CRO 843-321-8490 oncobaysites@oncobay.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05973487
Other Study ID Numbers  ICMJE TSCAN-002
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party TScan Therapeutics, Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE TScan Therapeutics, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Dawn Pinchasik, MD TScan Therapeutics
PRS Account TScan Therapeutics, Inc.
Verification Date May 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP