A Basket Study of Customized Autologous TCR-T Cell Therapies in Patients With Locally Advanced (Unresectable) or Metastatic Solid Tumors

November 14, 2025 updated by: TScan Therapeutics, Inc.

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

TScan Therapeutics is developing cellular therapies across multiple solid tumors in which autologous participant-derived engeneered 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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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
  • COHORT G: TSC-202-A0201 targeting MAGE-A4 on HLA-A*02:01

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
  • COHORT AG: TSC-204-A0201 + TSC-202-A0201
  • COHORT BG: TSC-204-C0702 + TSC-202-A0201
  • COHORT CG: TSC-200-A0201 + TSC-202-A0201
  • COHORT DG: TSC-203-A0201 + TSC-202-A0201
  • COHORT EG: TSC-204-A0101 + TSC-202-A0201
  • COHORT FG: TSC-201-B0702 + TSC-202-A0201

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

Interventional

Enrollment (Estimated)

840

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85258
        • HonorHealth Research and Innovation Institute
    • California
      • San Diego, California, United States, 92037
        • University of California San Diego
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale Cancer Center
    • Florida
      • Hollywood, Florida, United States, 33021
        • Memorial healthcare System
      • Miami, Florida, United States, 33136
        • University of Miami, Sylvester Comprehensive Cancer Center
      • Orlando, Florida, United States, 32806
        • Orlando Health
      • Tampa, Florida, United States, 33606
        • University of South Florida
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Norton Cancer Institute
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Institute
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota Masonic Cancer Center
    • New York
      • New York, New York, United States, 10032
        • Columbia University Herbert Irving Comprehensive Cancer Center
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina at Chapel Hill
    • Ohio
      • Cincinnati, Ohio, United States, 45242
        • Oncology Hematology Care
      • Cleveland, Ohio, United States, 44195
        • The Cleveland Clinic
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • OU Health Stephenson Cancer Center
    • Oregon
      • Portland, Oregon, United States, 97213
        • Providence Cancer Institute Franz Clinic
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburgh Medical Center
      • Pittsburgh, Pennsylvania, United States, 15224
        • Allegheny Hospitals Network
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute
    • Texas
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 and/or HLA-A*02:01
  5. Tumor must express one or more of the following: MAGE-A1, MAGE-A4, MAGE-C2, PRAME and HPV16 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. Have a history of ASTCT Grade 4 CRS, Grade 3 or greater ICANS, or Grade 3 or greater IECHS. Participants with a history of lower grade CRS, ICANS, or IECHS may be eligible, pending review and approval by the Medical Monitor.
  4. History of stroke or transient ischemic attack (TIA) within 6 months of enrollment
  5. Systemic corticosteroid therapy >10 mg of prednisone daily or equivalent within 7 days of enrollment.
  6. History of severe hypersensitivity to fludarabine or cyclophosphamide or study product excipients including human serum albumin, Cryostor (DMSO or Dextran 40), or Plasma-Lyte.
  7. Untreated or symptomatic central nervous system (CNS) metastases or cytology proven carcinomatous meningitis.
  8. Concurrent receipt of another anti-cancer therapy. Have a history of acute mental status changes of unknown etiology within 6 months prior to enrollment, or any neurological or neurodegenerative disorder (e.g., Parkinson disease, Huntington disease, uncontrolled seizure disorder) that may increase the risk for or confound the assessment of neurotoxicity.
  9. Presence of fungal, bacterial, viral, or other infection requiring anti-microbials for management.
  10. 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.
  11. Participants who regularly require supplemental oxygen.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Monotherapy Cohort A
TSC-204-A0201
Biological: TSC-204-A0201
Escalating doses of TSC-204-A0201 as a monotherapy
Experimental: Monotherapy Cohort B
TSC-204-C0702
Biological: TSC-204-C0702
Escalating doses of TSC-204-C0702 as a monotherapy
Experimental: Monotherapy Cohort C
TSC-200-A0201
Biological: TSC-200-A0201
Escalating doses of TSC-200-A0201 as a monotherapy
Experimental: T-Plex Combination Cohort A + B
TSC-204-A0201 and TSC-204-C0702
Biological: TSC-204-A0201 + TSC-204-C0702
Escalating doses of TSC-204-A0201 in combination with TSC-204-C0702
Experimental: T-Plex Combination Cohort B + C
TSC-204-C0702 and TSC-200-A0201
Biological: TSC-204-A0201 + TSC-200-A0201
Escalating doses of TSC-204-A0201 in combination with TSC-200-A0201
Experimental: T-Plex Combination Cohort A + C
TSC-204-A0201 and TSC-200-A0201
Biological: TSC-204-C0702 + TSC-200-A0201
Escalating doses of TSC-204-C0702 in combination with TSC-200-A0201
Experimental: Monotherapy Cohort D
TSC-203-A0201
Biological: TSC-203-A0201
Escalating doses of TSC-203-A0201 as a monotherapy
Experimental: T-Plex Combination Cohort A + D
TSC-204-A0201 + TSC-203-A0201
Biological: TSC-204-A0201 + TSC-203-A0201
Escalating doses of TSC-204-A0201 in combination with TSC-203-A0201
Experimental: T-Plex Combination Cohort B + D
TSC-204-C0702 + TSC-203-A0201
Biological: TSC-204-C0702 + TSC-203-A0201
Escalating doses of TSC-204-C0702 in combination with TSC-203-A0201
Experimental: T-Plex Combination Cohort C + D
TSC-200-A0201 + TSC-203-A0201
Biological: TSC-200-A0201 + TSC-203-A0201
Escalating doses of TSC-200-A0201 in combination with TSC-203-A0201
Experimental: Monotherapy Cohort E
TSC-204-A0101
Biological: TSC-204-A0101
Escalating doses of TSC-204-A0101 as a monotherapy
Experimental: Monotherapy Cohort F
TSC-201-B0702
Biological: TSC-201-B0702
Escalating doses of TSC-201-B0702 as a monotherapy
Experimental: T-Plex Combination Cohort A + E
TSC-204-A0201 + TSC-204-A0101
Biological: TSC-204-A0201 + TSC-204-A0101
Escalating doses of TSC-204-A0201 in combination with TSC-204-A0101
Experimental: T-Plex Combination Cohort A + F
TSC-204-A0201 + TSC-201-B0702
Biological: TSC-204-A0201 + TSC-201-B0702
Escalating doses of TSC-204-A0201 in combination with TSC-201-B0702
Experimental: T-Plex Combination Cohort B + E
TSC-204-C0702 + TSC-204-A0101
Biological: TSC-204-C0702 + TSC-204-A0101
Escalating doses of TSC-204-C0702 in combination with TSC-204-A0101
Experimental: T-Plex Combination Cohort B + F
TSC-204-C0702 + TSC-201B0702
Biological: TSC-204-C0702 + TSC-201-B0702
Escalating doses of TSC-204-C0702 in combination with TSC-201-B0702
Experimental: T-Plex Combination Cohort C + E
TSC-200-A0201 + TSC-204-A0101
Biological: TSC-200-A0201 + TSC-204-A0101
Escalating doses of TSC-200-A0201 in combination with TSC-204-A0101
Experimental: T-Plex Combination Cohort C + F
TSC-200-A0201 + TSC-201B0702
Biological: TSC-200-A0201 + TSC-201-B0702
Escalating doses of TSC-200-A0201 in combination with TSC-201-B0702
Experimental: T-Plex Combination Cohort D + E
TSC-203-A0201 + TSC-204A0101
Biological: TSC-203-A0201 + TSC-204-A0101
Escalating doses of TSC-203-A0201 in combination with TSC-204-A0101
Experimental: T-Plex Combination Cohort D + F
TSC-203-A0201 + TSC-201B0702
Biological: TSC-203-A0201 + TSC-201-B0702
Escalating doses of TSC-203-A0201 in combination with TSC-201-B0702
Experimental: T-Plex Combination Cohort E + F
TSC-204-A0101 + TSC-201-B0702
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
Experimental: Monotherapy Cohort G
TSC-202-A0201
Biological: TSC-202-A0201
Escalating doses of TSC-202-A0201 as a monotherapy
Experimental: T-Plex Combination Cohort A + G
TSC-204-A0201 + TSC-202-A0201
Biological: TSC-204-A0201 + TSC-202-A0201
Escalating doses of TSC-204-A0201 in combination with TSC-202-A0201
Experimental: T-Plex Combination Cohort B + G
TSC-204-C0702 + TSC-202-A0201
Biological: TSC-204-C0702 + TSC-202-A0201
Escalating doses of TSC-204-C0702 in combination with TSC-202-A0201
Experimental: T-Plex Combination Cohort C+ G
TSC-200-A0201 + TSC-202-A0201
Biological: TSC-200-A0201 + TSC-202-A0201
Escalating doses of TSC-200-A0201 in combination with TSC-202-A0201
Experimental: T-Plex Combination Cohort D + G
TSC-203-A0201 + TSC-202-A0201
Biological: TSC-203-A0201 + TSC-202-A0201
Escalating doses of TSC-203-A0201 in combination with TSC-202-A0201
Experimental: T-Plex Combination Cohort E + G
TSC-204-A0101 + TSC-202-A0201
Biological: TSC-204-A0101 + TSC-202-A0201
Escalating doses of TSC-204-A0101 in combination with TSC-202-A0201
Experimental: T-Plex Combination Cohort F + G
TSC-201-B0702 + TSC-202-A0201
Biological: TSC-201-B0702 + TSC-202-A0201
Escalating doses of TSC-201-B0702 in combination with TSC-202-A0201

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate the safety of monotherapy and T- Plex combination TCR-Ts
Time Frame: 28 days
Number of subjects with dose limiting toxicities (DLT)
28 days
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
Up to 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Up to 12 months
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
Up to 12 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Up to 24 months
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
Up to 24 months
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
Up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

TScan Therapeutics, Inc.

Investigators

  • Study Director: Dawn Pinchasik, MD, Tscan Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 6, 2024

Primary Completion (Estimated)

December 30, 2026

Study Completion (Estimated)

December 30, 2026

Study Registration Dates

First Submitted

July 25, 2023

First Submitted That Met QC Criteria

August 1, 2023

First Posted (Actual)

August 3, 2023

Study Record Updates

Last Update Posted (Actual)

November 17, 2025

Last Update Submitted That Met QC Criteria

November 14, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TSCAN-002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Melanoma

Clinical Trials on TSC-204-A0201

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in United Arab Emirates

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe