A Phase 1/3 Study Evaluating the Efficacy and Safety of T-Cell Receptor Engineered Donor T Cells in Subjects Undergoing Allogeneic Peripheral Blood Stem Cell Transplantation
This is a multicenter, genetically-randomized, controlled, Phase 3 study evaluating the efficacy and safety of T-cell receptor-engineered donor T cells targeting HA-2 (TSC-101) administered following reduced-intensity conditioning (RIC) hematopoietic cell transplantation (HCT) in participants with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). The study will compare TSC-101 plus standard of care (SOC) versus SOC alone in participants undergoing allogeneic peripheral blood stem cell transplantation from haploidentical or mismatched unrelated donors.
• Patient aged ≥ 18 years at the time of signing informed consent.
• Karnofsky Performance Status (KPS) ≥50 at the time of the screening visit.
• Undergoing first allo-HCT with a diagnosis of:
‣ AML with bone marrow blasts \< 5%, absence of circulating blasts, and absence of extramedullary disease.
⁃ MDS
• Must express HLA-A\*02:01 as determined by pre-transplant institutional SOC work-up to be eligible for the treatment arm.
• Must have the HA-2 positive genotype to be eligible for the treatment arm.
• Undergoing RIC HCT using a haplo donor or MMUD.
‣ Donors for treatment-arm subjects must be HLA-A\*02-negative.
⁃ Donors for control-arm subjects do not have to be HLA-A\*02-negative.
• Undergoing use of PTCy for GvHD prophylaxis at standard doses.
• Use of peripheral blood stem cell source.
• Organ function parameters for transplant eligibility are met per institutional standards. Where organ function may fall outside of institutional standard for transplant, and patient is still proceeding to transplant, the case should be reviewed and approved by the MedicalMonitor.
⁃ Patient or legally authorized representative (LAR) capable of giving signed informed consent and willingness to comply with the requirements and restrictions listed in the informed consent form (ICF) and clinical protocol.
⁃ Agrees to participate in long-term follow-up (LTFU) for up to 15 years post the final infusion of TSC-101 if they receive a TSC-101 infusion.
⁃ Contraceptive use by male and female subjects must be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. At a minimum:
∙ A male subject must agree to use a highly effective contraceptive during the intervention period and for at least 12 months after the last TSC-101 infusion and refrain from donating sperm during this period.
‣ A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
⁃ Not a woman of childbearing potential (WOCBP) as defined in Appendix 2 OR
• A WOCBP who agrees to follow the contraceptive guidance in Appendix 2 during the intervention period and for at least 12 months after the last TSC-101 infusion.
• Male or female ≥ 50 kg and aged ≥ 16 years at the time of signing informed consent who meet the criteria to donate as per the institutional SOC.
• Capable of giving signed informed consent, or assent/parental consent per institutional SOC, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
• For treatment-arm donors: able to undergo peripheral blood stem cell (PBSC) collection and at least 2 rounds of leukapheresis (for both TSC-101 manufacturing and the stem cell collection for HCT).
• For treatment-arm donors: negative for all HLA-A\*02 alleles • Donors for control-arm subjects do not have to be negative for HLA-A\*02 alleles.