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

Sponsor

TScan Therapeutics, Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05973487

Collaborator

(none)

100

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

1.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Biological: TSC-204-A0201 Biological: TSC-204-C0702 Biological: TSC-200-A0201 Biological: TSC-204-A0201 + TSC-204-C0702 Biological: TSC-204-A0201 + TSC-200-A0201 Biological: TSC-204-A0201 + TSC-200-A0201	Phase 1

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

T-Plex Combination:

Cohort AB: TSC-204-A0201 + TSC-204-C0702
Cohort BC: TSC-204-A0201 + TSC-200-A0201
Cohort AC: TSC-204-C0702 + TSC-200-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 Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Aug 31, 2023

Anticipated Primary Completion Date :

Dec 30, 2026

Anticipated Study Completion Date :

Dec 30, 2026

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Evaluate the safety of monotherapy and T- Plex combination TCR-Ts [28 days]
Number of subjects with dose limiting toxicities (DLT)
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

Secondary Outcome Measures

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

Other Outcome Measures

To measure the persistence of T-Plex TCR-T cells in the peripheral blood with single and repeat doses [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 [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 [Up to 24 months]
Status of immune activation markers in the tumor after single and repeat doses

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Must be at least 18 years.
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.
Any solid tumor, 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.
Participants must express one of the following HLA types, as assessed by a qualified genomics assay in screening study TSCAN-003: HLA-C07:02, HLA-A02:01 and HLA-C07:02 plus HLA-A02:01
Tumor must express MAGE-A1 and/or HPV16-E7 as assessed by a qualified IHC or RNA-ISH performed in the last 6 months in screening study TSCAN-003 (NCT05812027).
Eastern Cooperative Oncology Group (ECOG) Performance status 0-1 at screening.
Participants must be able to understand and be willing to give informed consent; decision-impaired adults may consent with their legally authorized representative.
At least 1 measurable lesion per modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Adequate bone marrow and organ function.

Exclusion Criteria:

Medical or psychological conditions that would make the participant unsuitable candidate for cell therapy at the discretion of the PI.
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
History of stroke or transient ischemic attack (TIA) within 12 months of enrollment
Systemic corticosteroid therapy >10 mg of prednisone daily or equivalent within 7 days of enrollment
History of severe hypersensitivity to fludarabine or cyclophosphamide or study product excipients including human serum albumin, Cryostor (DMSO or Dextran 40), or Plasma-Lyte.
Untreated or symptomatic central nervous system (CNS) metastases or cytology proven carcinomatous meningitis.
Concurrent receipt of another anti-cancer therapy.
Presence of fungal, bacterial, viral, or other infection requiring anti-microbials for management.
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.
Participants who regularly require supplemental oxygen.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	HonorHealth Research and Innovation Institute	Scottsdale	Arizona	United States	85258
2	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599