Anogenital Cancers, Cervical Cancer, Head and Neck Cancer, HPV - Anogenital Human Papilloma Virus Infection, HPV-Associated Vaginal Adenocarcinoma, HPV Positive Oropharyngeal Squamous Cell Carcinoma, HPV Positive Rectal Squamous Cell Carcinoma, HPV-Related Adenocarcinoma, HPV-Related Adenosquamous Carcinoma, HPV-Related Anal Squamous Cell Carcinoma, HPV-Related Carcinoma, HPV-Related Cervical Carcinoma, HPV-Related Endocervical Adenocarcinoma, HPV-Related Malignancy, HPV-Related Penile Squamous Cell Carcinoma, HPV-Related Squamous Cell Carcinoma, HPV-Related Verrucous Carcinoma, HPV-Related Vulvar Squamous Cell Carcinoma, Melanoma, Non-small Cell Carcinoma, Ovarian Cancer
Conditions
Keywords
HPV16 E7, MAGE-A1, TCR-T Therapy, Cell Therapy, Immunotherapy, TScan Therapeutics, TSCAN-002, TSCAN-003, PRAME, MAGE-C2, MAGE-A4
Brief summary
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
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).
Interventions
BIOLOGICALTSC-204-A0201
Escalating doses of TSC-204-A0201 as a monotherapy
BIOLOGICALTSC-204-C0702
Escalating doses of TSC-204-C0702 as a monotherapy
BIOLOGICALTSC-200-A0201
Escalating doses of TSC-200-A0201 as a monotherapy
BIOLOGICALTSC-204-A0201 + TSC-204-C0702
Escalating doses of TSC-204-A0201 in combination with TSC-204-C0702
BIOLOGICALTSC-204-A0201 + TSC-200-A0201
Escalating doses of TSC-204-A0201 in combination with TSC-200-A0201
BIOLOGICALTSC-204-C0702 + TSC-200-A0201
Escalating doses of TSC-204-C0702 in combination with TSC-200-A0201
BIOLOGICALTSC-204-A0201 + TSC-203-A0201
Escalating doses of TSC-204-A0201 in combination with TSC-203-A0201
BIOLOGICALTSC-204-C0702 + TSC-203-A0201
Escalating doses of TSC-204-C0702 in combination with TSC-203-A0201
BIOLOGICALTSC-200-A0201 + TSC-203-A0201
Escalating doses of TSC-200-A0201 in combination with TSC-203-A0201
BIOLOGICALTSC-203-A0201
Escalating doses of TSC-203-A0201 as a monotherapy
BIOLOGICALTSC-204-A0101
Escalating doses of TSC-204-A0101 as a monotherapy
BIOLOGICALTSC-201-B0702
Escalating doses of TSC-201-B0702 as a monotherapy
BIOLOGICALTSC-204-A0201 + TSC-204-A0101
Escalating doses of TSC-204-A0201 in combination with TSC-204-A0101
BIOLOGICALTSC-204-A0201 + TSC-201-B0702
Escalating doses of TSC-204-A0201 in combination with TSC-201-B0702
BIOLOGICALTSC-204-C0702 + TSC-204-A0101
Escalating doses of TSC-204-C0702 in combination with TSC-204-A0101
BIOLOGICALTSC-204-C0702 + TSC-201-B0702
Escalating doses of TSC-204-C0702 in combination with TSC-201-B0702
BIOLOGICALTSC-200-A0201 + TSC-204-A0101
Escalating doses of TSC-200-A0201 in combination with TSC-204-A0101
BIOLOGICALTSC-200-A0201 + TSC-201-B0702
Escalating doses of TSC-200-A0201 in combination with TSC-201-B0702
BIOLOGICALTSC-203-A0201 + TSC-204-A0101
Escalating doses of TSC-203-A0201 in combination with TSC-204-A0101
BIOLOGICALTSC-203-A0201 + TSC-201-B0702
Escalating doses of TSC-203-A0201 in combination with TSC-201-B0702
BIOLOGICALTSC-202-A0201
Escalating doses of TSC-202-A0201 as a monotherapy
BIOLOGICALTSC-204-A0201 + TSC-202-A0201
Escalating doses of TSC-204-A0201 in combination with TSC-202-A0201
BIOLOGICALTSC-204-C0702 + TSC-202-A0201
Escalating doses of TSC-204-C0702 in combination with TSC-202-A0201
BIOLOGICALTSC-200-A0201 + TSC-202-A0201
Escalating doses of TSC-200-A0201 in combination with TSC-202-A0201
BIOLOGICALTSC-203-A0201 + TSC-202-A0201
Escalating doses of TSC-203-A0201 in combination with TSC-202-A0201
BIOLOGICALTSC-204-A0101 + TSC-202-A0201
Escalating doses of TSC-204-A0101 in combination with TSC-202-A0201
BIOLOGICALTSC-201-B0702 + TSC-202-A0201
Escalating doses of TSC-201-B0702 in combination with TSC-202-A0201
Sponsors
TScan Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
Countries
United States
Outcome results
None listed