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

Phase 1

Recruiting

• Conditions: HPV - Anogenital Human Papilloma Virus Infection; HPV-Related Squamous Cell Carcinoma; HPV-Related Endocervical Adenocarcinoma; HPV-Related Anal Squamous Cell Carcinoma; HPV-Related Penile Squamous Cell Carcinoma; HPV-Related Vulvar Squamous Cell Carcinoma; HPV Positive Rectal Squamous Cell Carcinoma; HPV-Related Cervical Carcinoma; HPV-Associated Vaginal Adenocarcinoma; Melanoma
• Interventions: Biological: TSC-204-A0201; Biological: TSC-200-A0201; Biological: TSC-204-A0201 + TSC-200-A0201; Biological: TSC-204-A0201 + TSC-204-A0101; Biological: TSC-204-C0702; Biological: TSC-204-A0201 + TSC-204-C0702; Biological: TSC-204-C0702 + TSC-203-A0201; Biological: TSC-204-A0101; Biological: TSC-200-A0201 + TSC-203-A0201; Biological: TSC-204-A0201 + TSC-201-B0702; Biological: TSC-204-C0702 + TSC-201-B0702; Biological: TSC-204-C0702 + TSC-200-A0201; Biological: TSC-203-A0201; Biological: TSC-204-A0201 + TSC-203-A0201; Biological: TSC-204-C0702 + TSC-204-A0101; Biological: TSC-203-A0201 + TSC-201-B0702; Biological: TSC-200-A0201 + TSC-204-A0101; Biological: TSC-200-A0201 + TSC-201-B0702; Biological: TSC-203-A0201 + TSC-204-A0101; Biological: TSC-201-B0702

• Registration Number: NCT05973487
• Lead Sponsor: TScan Therapeutics, Inc.

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 Timeline

• Study First Submitted: 2023-07-25
• Study First Submitted QC: 2023-08-01
• Study First Posted: 2023-08-03
• Study Start: 2024-05-06
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-22
• Last Update Posted: 2024-08-26
• Primary Completion: 2026-12-30
• Study Completion: 2026-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Monotherapy Cohort A	TSC-204-A0201	TSC-204-A0201
Monotherapy Cohort C	TSC-200-A0201	TSC-200-A0201
T-Plex Combination Cohort E + F	TSC-201-B0702	TSC-204-A0101 + TSC-201-B0702
T-Plex Combination Cohort B + C	TSC-204-A0201 + TSC-200-A0201	TSC-204-C0702 and TSC-200-A0201
T-Plex Combination Cohort A + E	TSC-204-A0201 + TSC-204-A0101	TSC-204-A0201 + TSC-204-A0101
Monotherapy Cohort B	TSC-204-C0702	TSC-204-C0702
T-Plex Combination Cohort A + B	TSC-204-A0201 + TSC-204-C0702	TSC-204-A0201 and TSC-204-C0702
T-Plex Combination Cohort B + D	TSC-204-C0702 + TSC-203-A0201	TSC-204-C0702 + TSC-203-A0201
Monotherapy Cohort E	TSC-204-A0101	TSC-204-A0101
T-Plex Combination Cohort C + D	TSC-200-A0201 + TSC-203-A0201	TSC-200-A0201 + TSC-203-A0201
T-Plex Combination Cohort A + F	TSC-204-A0201 + TSC-201-B0702	TSC-204-A0201 + TSC-201-B0702
T-Plex Combination Cohort B + F	TSC-204-C0702 + TSC-201-B0702	TSC-204-C0702 + TSC-201B0702
T-Plex Combination Cohort A + C	TSC-204-C0702 + TSC-200-A0201	TSC-204-A0201 and TSC-200-A0201
Monotherapy Cohort D	TSC-203-A0201	TSC-203-A0201
T-Plex Combination Cohort A + D	TSC-204-A0201 + TSC-203-A0201	TSC-204-A0201 + TSC-203-A0201
Monotherapy Cohort F	TSC-201-B0702	TSC-201-B0702
T-Plex Combination Cohort B + E	TSC-204-C0702 + TSC-204-A0101	TSC-204-C0702 + TSC-204-A0101
T-Plex Combination Cohort D + F	TSC-203-A0201 + TSC-201-B0702	TSC-203-A0201 + TSC-201B0702
T-Plex Combination Cohort C + E	TSC-200-A0201 + TSC-204-A0101	TSC-200-A0201 + TSC-204-A0101
T-Plex Combination Cohort C + F	TSC-200-A0201 + TSC-201-B0702	TSC-200-A0201 + TSC-201B0702
T-Plex Combination Cohort D + E	TSC-203-A0201 + TSC-204-A0101	TSC-203-A0201 + TSC-204A0101
T-Plex Combination Cohort E + F	TSC-204-A0101	TSC-204-A0101 + TSC-201-B0702

Primary Outcome Measures

Name	Time	Method
Determine the recommended phase 2 dose of monotherapy and T- Plex combination TCR-Ts	Up to 12 months	Frequency and severity of DLTs, AEs and SAEs
Evaluate the safety of monotherapy and T- Plex combination TCR-Ts	28 days	Number of subjects with dose limiting toxicities (DLT)

Secondary Outcome Measures

Name	Time	Method
Investigate preliminary anti-tumor activity of monotherapy and T- Plex combination TCR-Ts	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	Up to 12 months	Frequency and severity of DLTs, AEs and SAEs

Trial Locations

Locations (15)

HonorHealth Research and Innovation Institute; 🇺🇸 Scottsdale, Arizona, United States

Memorial Healthcare System; 🇺🇸 Hollywood, Florida, United States

University of Miami, Sylvester Comprehensive Cancer Center; 🇺🇸 Miami, Florida, United States

University of Minnesota Masonic Cancer Center; 🇺🇸 Minneapolis, Minnesota, United States

Columbia University Herbert Irving Comprehensive Cancer Center; 🇺🇸 New York, New York, United States

Allegheny Hospitals Network; 🇺🇸 Pittsburgh, Pennsylvania, United States

Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

OU Health Stephenson Cancer Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Providence Cancer Institute Franz Clinic; 🇺🇸 Portland, Oregon, United States

The Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

University of North Carolina at Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States

Orlando Health; 🇺🇸 Orlando, Florida, United States

Yale Cancer Center; 🇺🇸 New Haven, Connecticut, United States

Norton Cancer Institute; 🇺🇸 Louisville, Kentucky, United States