TScan Therapeutics doses first patient in Phase 3 ALLOHA-2 trial
TScan Therapeutics has dosed its first patient in the Phase 3 ALLOHA-2 pivotal trial, evaluating TSC-101, its T cell receptor-engineered T cell (TCR-T) therapy, for prevention of relapse following allogeneic haematopoietic cell transplantation (allo-HCT) in patients with acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). The patient, enrolled in June, received their first TSC-101 infusion after successful stem cell engraftment.
The milestone marks the transition of TSC-101 from Phase 1 into a pivotal setting. Gavin MacBeath, chief executive officer of TScan, said dosing the first ALLOHA-2 patient acknowledged "all the hard work that went into bringing TSC-101 to this integral step," and pointed to data from Cohort C of the earlier Phase 1 ALLOHA trial as the basis for confidence in the Phase 3 design. Cohort C used TScan's commercial-ready manufacturing process, and MacBeath said the efficacy and safety results from that cohort strengthened the company's forward-looking plans.
Trial design and endpoints
ALLOHA-2 (NCT07702578) employs a biological assignment strategy rather than conventional randomisation. Subjects who are HLA-A02:01-positive and have a suitable donor are assigned to the treatment arm and receive two TSC-101 infusions following engraftment on top of standard reduced-intensity conditioning HCT. Patients who are A02:01-negative, or A02:01-positive without a matched donor, are assigned to the control arm receiving HCT alone. The primary endpoint is relapse-free survival, with overall survival and event-free survival as key secondary measures. This genetic assignment approach reflects TSC-101's mechanism, which targets a peptide presented by the HLA-A02:01 allele.
Chief medical officer Chrystal Louis said TSC-101's safety profile and clinical results "continue to excite the transplant community," and cited the pace of Cohort C enrolment as evidence of growing clinical interest in the asset.
Market context and competitive landscape
Post-transplant relapse remains one of the most clinically urgent unmet needs in haematological oncology. Allo-HCT offers potential cure in AML and MDS, but relapse rates after transplantation remain high, and approved options to prevent or treat post-transplant relapse are limited. Maintenance strategies using hypomethylating agents such as azacitidine have shown modest benefit, while the FLT3 inhibitor gilteritinib is under investigation in the post-transplant setting, though neither is universally applicable across AML and MDS subtypes.
TCR-T therapies occupy a distinct niche from the CAR-T approaches that have transformed relapsed and refractory haematological oncology over the past decade. Where CAR-T products typically target surface antigens such as CD19 or BCMA, TCR-based approaches can target intracellular peptides presented via MHC, broadening the addressable antigen landscape. TScan is one of a small number of companies pursuing TCR-T in the post-transplant setting, and ALLOHA-2 is among the more advanced pivotal programmes in this modality for AML and MDS.
The company also disclosed that it is in early-stage development of in vivo engineering methods for solid tumours and is applying its target discovery platform to autoimmune disorders, suggesting it intends to expand beyond the current haematology focus over the longer term.
Near-term attention will focus on enrolment pace in ALLOHA-2 and whether the relapse-free survival signal from Phase 1 Cohort C translates into a statistically meaningful benefit in the pivotal setting. Nasdaq-listed TScan (TCRX) has not disclosed a targeted enrolment number or anticipated primary completion date in the current release.