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

NCT ID: NCT05973487

Last Updated: 2025-11-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

840 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-05-06

Study Completion Date

2026-12-30

Brief Summary

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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.

Detailed Description

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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).

Conditions

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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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Monotherapy Cohort A

TSC-204-A0201

Group Type EXPERIMENTAL

TSC-204-A0201

Intervention Type BIOLOGICAL

Escalating doses of TSC-204-A0201 as a monotherapy

Monotherapy Cohort B

TSC-204-C0702

Group Type EXPERIMENTAL

TSC-204-C0702

Intervention Type BIOLOGICAL

Escalating doses of TSC-204-C0702 as a monotherapy

Monotherapy Cohort C

TSC-200-A0201

Group Type EXPERIMENTAL

TSC-200-A0201

Intervention Type BIOLOGICAL

Escalating doses of TSC-200-A0201 as a monotherapy

T-Plex Combination Cohort A + B

TSC-204-A0201 and TSC-204-C0702

Group Type EXPERIMENTAL

TSC-204-A0201 + TSC-204-C0702

Intervention Type BIOLOGICAL

Escalating doses of TSC-204-A0201 in combination with TSC-204-C0702

T-Plex Combination Cohort B + C

TSC-204-C0702 and TSC-200-A0201

Group Type EXPERIMENTAL

TSC-204-A0201 + TSC-200-A0201

Intervention Type BIOLOGICAL

Escalating doses of TSC-204-A0201 in combination with TSC-200-A0201

T-Plex Combination Cohort A + C

TSC-204-A0201 and TSC-200-A0201

Group Type EXPERIMENTAL

TSC-204-C0702 + TSC-200-A0201

Intervention Type BIOLOGICAL

Escalating doses of TSC-204-C0702 in combination with TSC-200-A0201

Monotherapy Cohort D

TSC-203-A0201

Group Type EXPERIMENTAL

TSC-203-A0201

Intervention Type BIOLOGICAL

Escalating doses of TSC-203-A0201 as a monotherapy

T-Plex Combination Cohort A + D

TSC-204-A0201 + TSC-203-A0201

Group Type EXPERIMENTAL

TSC-204-A0201 + TSC-203-A0201

Intervention Type BIOLOGICAL

Escalating doses of TSC-204-A0201 in combination with TSC-203-A0201

T-Plex Combination Cohort B + D

TSC-204-C0702 + TSC-203-A0201

Group Type EXPERIMENTAL

TSC-204-C0702 + TSC-203-A0201

Intervention Type BIOLOGICAL

Escalating doses of TSC-204-C0702 in combination with TSC-203-A0201

Monotherapy Cohort E

TSC-204-A0101

Group Type EXPERIMENTAL

TSC-204-A0101

Intervention Type BIOLOGICAL

Escalating doses of TSC-204-A0101 as a monotherapy

Monotherapy Cohort F

TSC-201-B0702

Group Type EXPERIMENTAL

TSC-201-B0702

Intervention Type BIOLOGICAL

Escalating doses of TSC-201-B0702 as a monotherapy

T-Plex Combination Cohort A + E

TSC-204-A0201 + TSC-204-A0101

Group Type EXPERIMENTAL

TSC-204-A0201 + TSC-204-A0101

Intervention Type BIOLOGICAL

Escalating doses of TSC-204-A0201 in combination with TSC-204-A0101

T-Plex Combination Cohort A + F

TSC-204-A0201 + TSC-201-B0702

Group Type EXPERIMENTAL

TSC-204-A0201 + TSC-201-B0702

Intervention Type BIOLOGICAL

Escalating doses of TSC-204-A0201 in combination with TSC-201-B0702

T-Plex Combination Cohort B + E

TSC-204-C0702 + TSC-204-A0101

Group Type EXPERIMENTAL

TSC-204-C0702 + TSC-204-A0101

Intervention Type BIOLOGICAL

Escalating doses of TSC-204-C0702 in combination with TSC-204-A0101

T-Plex Combination Cohort B + F

TSC-204-C0702 + TSC-201B0702

Group Type EXPERIMENTAL

TSC-204-C0702 + TSC-201-B0702

Intervention Type BIOLOGICAL

Escalating doses of TSC-204-C0702 in combination with TSC-201-B0702

T-Plex Combination Cohort C + D

TSC-200-A0201 + TSC-203-A0201

Group Type EXPERIMENTAL

TSC-200-A0201 + TSC-203-A0201

Intervention Type BIOLOGICAL

Escalating doses of TSC-200-A0201 in combination with TSC-203-A0201

T-Plex Combination Cohort C + E

TSC-200-A0201 + TSC-204-A0101

Group Type EXPERIMENTAL

TSC-200-A0201 + TSC-204-A0101

Intervention Type BIOLOGICAL

Escalating doses of TSC-200-A0201 in combination with TSC-204-A0101

T-Plex Combination Cohort C + F

TSC-200-A0201 + TSC-201B0702

Group Type EXPERIMENTAL

TSC-200-A0201 + TSC-201-B0702

Intervention Type BIOLOGICAL

Escalating doses of TSC-200-A0201 in combination with TSC-201-B0702

T-Plex Combination Cohort D + E

TSC-203-A0201 + TSC-204A0101

Group Type EXPERIMENTAL

TSC-203-A0201 + TSC-204-A0101

Intervention Type BIOLOGICAL

Escalating doses of TSC-203-A0201 in combination with TSC-204-A0101

T-Plex Combination Cohort D + F

TSC-203-A0201 + TSC-201B0702

Group Type EXPERIMENTAL

TSC-203-A0201 + TSC-201-B0702

Intervention Type BIOLOGICAL

Escalating doses of TSC-203-A0201 in combination with TSC-201-B0702

T-Plex Combination Cohort E + F

TSC-204-A0101 + TSC-201-B0702

Group Type EXPERIMENTAL

TSC-204-A0101

Intervention Type BIOLOGICAL

Escalating doses of TSC-204-A0101 as a monotherapy

TSC-201-B0702

Intervention Type BIOLOGICAL

Escalating doses of TSC-201-B0702 as a monotherapy

Monotherapy Cohort G

TSC-202-A0201

Group Type EXPERIMENTAL

TSC-202-A0201

Intervention Type BIOLOGICAL

Escalating doses of TSC-202-A0201 as a monotherapy

T-Plex Combination Cohort A + G

TSC-204-A0201 + TSC-202-A0201

Group Type EXPERIMENTAL

TSC-204-A0201 + TSC-202-A0201

Intervention Type BIOLOGICAL

Escalating doses of TSC-204-A0201 in combination with TSC-202-A0201

T-Plex Combination Cohort B + G

TSC-204-C0702 + TSC-202-A0201

Group Type EXPERIMENTAL

TSC-204-C0702 + TSC-202-A0201

Intervention Type BIOLOGICAL

Escalating doses of TSC-204-C0702 in combination with TSC-202-A0201

T-Plex Combination Cohort C+ G

TSC-200-A0201 + TSC-202-A0201

Group Type EXPERIMENTAL

TSC-200-A0201 + TSC-202-A0201

Intervention Type BIOLOGICAL

Escalating doses of TSC-200-A0201 in combination with TSC-202-A0201

T-Plex Combination Cohort D + G

TSC-203-A0201 + TSC-202-A0201

Group Type EXPERIMENTAL

TSC-203-A0201 + TSC-202-A0201

Intervention Type BIOLOGICAL

Escalating doses of TSC-203-A0201 in combination with TSC-202-A0201

T-Plex Combination Cohort E + G

TSC-204-A0101 + TSC-202-A0201

Group Type EXPERIMENTAL

TSC-204-A0101 + TSC-202-A0201

Intervention Type BIOLOGICAL

Escalating doses of TSC-204-A0101 in combination with TSC-202-A0201

T-Plex Combination Cohort F + G

TSC-201-B0702 + TSC-202-A0201

Group Type EXPERIMENTAL

TSC-201-B0702 + TSC-202-A0201

Intervention Type BIOLOGICAL

Escalating doses of TSC-201-B0702 in combination with TSC-202-A0201

Interventions

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TSC-204-A0201

Escalating doses of TSC-204-A0201 as a monotherapy

Intervention Type BIOLOGICAL

TSC-204-C0702

Escalating doses of TSC-204-C0702 as a monotherapy

Intervention Type BIOLOGICAL

TSC-200-A0201

Escalating doses of TSC-200-A0201 as a monotherapy

Intervention Type BIOLOGICAL

TSC-204-A0201 + TSC-204-C0702

Escalating doses of TSC-204-A0201 in combination with TSC-204-C0702

Intervention Type BIOLOGICAL

TSC-204-A0201 + TSC-200-A0201

Escalating doses of TSC-204-A0201 in combination with TSC-200-A0201

Intervention Type BIOLOGICAL

TSC-204-C0702 + TSC-200-A0201

Escalating doses of TSC-204-C0702 in combination with TSC-200-A0201

Intervention Type BIOLOGICAL

TSC-204-A0201 + TSC-203-A0201

Escalating doses of TSC-204-A0201 in combination with TSC-203-A0201

Intervention Type BIOLOGICAL

TSC-204-C0702 + TSC-203-A0201

Escalating doses of TSC-204-C0702 in combination with TSC-203-A0201

Intervention Type BIOLOGICAL

TSC-200-A0201 + TSC-203-A0201

Escalating doses of TSC-200-A0201 in combination with TSC-203-A0201

Intervention Type BIOLOGICAL

TSC-203-A0201

Escalating doses of TSC-203-A0201 as a monotherapy

Intervention Type BIOLOGICAL

TSC-204-A0101

Escalating doses of TSC-204-A0101 as a monotherapy

Intervention Type BIOLOGICAL

TSC-201-B0702

Escalating doses of TSC-201-B0702 as a monotherapy

Intervention Type BIOLOGICAL

TSC-204-A0201 + TSC-204-A0101

Escalating doses of TSC-204-A0201 in combination with TSC-204-A0101

Intervention Type BIOLOGICAL

TSC-204-A0201 + TSC-201-B0702

Escalating doses of TSC-204-A0201 in combination with TSC-201-B0702

Intervention Type BIOLOGICAL

TSC-204-C0702 + TSC-204-A0101

Escalating doses of TSC-204-C0702 in combination with TSC-204-A0101

Intervention Type BIOLOGICAL

TSC-204-C0702 + TSC-201-B0702

Escalating doses of TSC-204-C0702 in combination with TSC-201-B0702

Intervention Type BIOLOGICAL

TSC-200-A0201 + TSC-204-A0101

Escalating doses of TSC-200-A0201 in combination with TSC-204-A0101

Intervention Type BIOLOGICAL

TSC-200-A0201 + TSC-201-B0702

Escalating doses of TSC-200-A0201 in combination with TSC-201-B0702

Intervention Type BIOLOGICAL

TSC-203-A0201 + TSC-204-A0101

Escalating doses of TSC-203-A0201 in combination with TSC-204-A0101

Intervention Type BIOLOGICAL

TSC-203-A0201 + TSC-201-B0702

Escalating doses of TSC-203-A0201 in combination with TSC-201-B0702

Intervention Type BIOLOGICAL

TSC-202-A0201

Escalating doses of TSC-202-A0201 as a monotherapy

Intervention Type BIOLOGICAL

TSC-204-A0201 + TSC-202-A0201

Escalating doses of TSC-204-A0201 in combination with TSC-202-A0201

Intervention Type BIOLOGICAL

TSC-204-C0702 + TSC-202-A0201

Escalating doses of TSC-204-C0702 in combination with TSC-202-A0201

Intervention Type BIOLOGICAL

TSC-200-A0201 + TSC-202-A0201

Escalating doses of TSC-200-A0201 in combination with TSC-202-A0201

Intervention Type BIOLOGICAL

TSC-203-A0201 + TSC-202-A0201

Escalating doses of TSC-203-A0201 in combination with TSC-202-A0201

Intervention Type BIOLOGICAL

TSC-204-A0101 + TSC-202-A0201

Escalating doses of TSC-204-A0101 in combination with TSC-202-A0201

Intervention Type BIOLOGICAL

TSC-201-B0702 + TSC-202-A0201

Escalating doses of TSC-201-B0702 in combination with TSC-202-A0201

Intervention Type BIOLOGICAL

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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TScan Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Dawn Pinchasik, MD

Role: STUDY_DIRECTOR

TScan Therapeutics

Locations

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HonorHealth Research and Innovation Institute

Scottsdale, Arizona, United States

Site Status

University of California San Diego

San Diego, California, United States

Site Status

Yale Cancer Center

New Haven, Connecticut, United States

Site Status

Memorial Healthcare System

Hollywood, Florida, United States

Site Status

University of Miami, Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Site Status

Orlando Health

Orlando, Florida, United States

Site Status

University of South Florida

Tampa, Florida, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Norton Cancer Institute

Louisville, Kentucky, United States

Site Status

Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

University of Minnesota Masonic Cancer Center

Minneapolis, Minnesota, United States

Site Status

Columbia University Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Site Status

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Oncology Hematology Care

Cincinnati, Ohio, United States

Site Status

The Cleveland Clinic

Cleveland, Ohio, United States

Site Status

OU Health Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Site Status

Providence Cancer Institute Franz Clinic

Portland, Oregon, United States

Site Status

Allegheny Hospitals Network

Pittsburgh, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

Countries

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United States

Other Identifiers

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TSCAN-002

Identifier Type: -

Identifier Source: org_study_id

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