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

Eligibility 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.
• 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.