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.
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
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
840
Escalating doses of TSC-204-A0201 as a monotherapy
Escalating doses of TSC-204-C0702 as a monotherapy
Escalating doses of TSC-200-A0201 as a monotherapy
Escalating doses of TSC-204-A0201 in combination with TSC-204-C0702
Escalating doses of TSC-204-A0201 in combination with TSC-200-A0201
Escalating doses of TSC-204-C0702 in combination with TSC-200-A0201
Escalating doses of TSC-204-A0201 in combination with TSC-203-A0201
Escalating doses of TSC-204-C0702 in combination with TSC-203-A0201
Escalating doses of TSC-200-A0201 in combination with TSC-203-A0201
Escalating doses of TSC-203-A0201 as a monotherapy
Escalating doses of TSC-204-A0101 as a monotherapy
Escalating doses of TSC-201-B0702 as a monotherapy
Escalating doses of TSC-204-A0201 in combination with TSC-204-A0101
Escalating doses of TSC-204-A0201 in combination with TSC-201-B0702
Escalating doses of TSC-204-C0702 in combination with TSC-204-A0101
Escalating doses of TSC-204-C0702 in combination with TSC-201-B0702
Escalating doses of TSC-200-A0201 in combination with TSC-204-A0101
Escalating doses of TSC-200-A0201 in combination with TSC-201-B0702
Escalating doses of TSC-203-A0201 in combination with TSC-204-A0101
Escalating doses of TSC-203-A0201 in combination with TSC-201-B0702
Escalating doses of TSC-202-A0201 as a monotherapy
Escalating doses of TSC-204-A0201 in combination with TSC-202-A0201
Escalating doses of TSC-204-C0702 in combination with TSC-202-A0201
Escalating doses of TSC-200-A0201 in combination with TSC-202-A0201
Escalating doses of TSC-203-A0201 in combination with TSC-202-A0201
Escalating doses of TSC-204-A0101 in combination with TSC-202-A0201
Escalating doses of TSC-201-B0702 in combination with TSC-202-A0201
HonorHealth Research and Innovation Institute
Scottsdale, Arizona, United States
University of California San Diego
San Diego, California, United States
Yale Cancer Center
New Haven, Connecticut, United States
Memorial Healthcare System
Hollywood, Florida, United States
University of Miami, Sylvester Comprehensive Cancer Center
Miami, Florida, United States
Orlando Health
Orlando, Florida, United States
University of South Florida
Tampa, Florida, United States
University of Chicago
Chicago, Illinois, United States
Norton Cancer Institute
Louisville, Kentucky, United States
Karmanos Cancer Institute
Detroit, Michigan, United States
...and 11 more locations
Evaluate the safety of monotherapy and T- Plex combination TCR-Ts
Number of subjects with dose limiting toxicities (DLT)
Time frame: 28 days
Determine the recommended phase 2 dose of monotherapy and T- Plex combination TCR-Ts
Frequency and severity of DLTs, AEs and SAEs
Time frame: Up to 12 months
Investigate preliminary anti-tumor activity of monotherapy and T- Plex combination TCR-Ts
Response Evaluation Criteria In Solid Tumors RECIST 1.1
Time frame: Up to 12 months
Investigate the feasibility of repeat dosing of monotherapy and T- Plex combination TCR-Ts
Frequency and severity of DLTs, AEs and SAEs
Time frame: Up to 12 months
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