Relapse-free survival favored TSC-101 over standard transplant alone in the Phase 1 ALLOHA study with a hazard ratio of 0.50 (p=0.23), and overall survival trended similarly (HR=0.61; p=0.52). At two years, 3 of 3 treated patients remained relapse-free versus 1 of 4 in the control arm. Relapse occurred in 4 of 19 treated patients versus 6 of 18 controls, corresponding to a relapse hazard ratio of 0.46 (p=0.22). In a high-risk TP53-mutated subset, 1 of 6 treated patients relapsed compared with 2 of 2 in the control arm who relapsed and subsequently died. TSC-101 was well tolerated with no dose-limiting toxicities reported.
TScan Therapeutics reported these updated ALLOHA data at ASH from 42 post–allogeneic HCT patients eligible for safety analysis, with treatment consisting of TSC-101 infusion after standard-of-care transplant compared with transplant alone. The company also disclosed that FDA has agreed to a pivotal study design mirroring the current Phase 1 approach and relying on a biologically assigned internal control, with pivotal initiation targeted for the second quarter of 2026. Operationally, TScan highlighted an updated “commercial-ready” manufacturing process that reduces production time from 17 to 12 days and limits ex vivo expansion, a parameter the company linked to mixed chimerism and relapse.
Strategically, TScan is pursuing a prevention thesis in a setting where relapse after allogeneic transplant remains a central failure mode and where randomized, placebo-controlled designs are often impractical. The choice to carry forward a biologically assigned internal control acknowledges both accrual realities and the heterogeneity of post-transplant care, while betting that directional survival advantages and a clean safety profile can be matured into a registrational data package. The manufacturing shift is equally strategic: shorter culture and reduced expansion aim to improve T-cell fitness and persistence while tightening vein-to-vein time around a narrow post-HCT window. Locking a fixed-dose regimen before pivotal readout is intended to simplify operations and standardize release criteria.
For transplant centers, the program adds a post-engraftment cell therapy step that will require coordination across apheresis, manufacturing scheduling, MRD assessment, chimerism monitoring, and immunosuppression management. Sites will need robust chain-of-identity and cryologistics capabilities and may benefit from the shorter 12-day cycle, but the process change will require training and clear comparability documentation. CROs and vendors supporting cellular therapy trials should anticipate complex scheduling and tighter data capture around MRD and chimerism endpoints. Regulators will focus on the credibility of the internal control, prespecified bias mitigation, and the alignment of primary endpoints—likely RFS—with clinically meaningful thresholds in this population. The TP53 signal, though based on small numbers, could influence stratification and subgroup analyses and may be relevant to potential expedited pathways.
What’s next is clarity on the pivotal protocol: endpoint hierarchy, event-driven assumptions, statistical powering, and the mechanics of biological assignment. Bridging to the revised manufacturing process will be a critical CMC inflection; the process used in the pivotal must be locked and comparable, with phenotype and potency assays aligned to clinical outcomes. Safety will remain under the microscope, particularly any signals related to graft-versus-host disease, immune reconstitution, or cytopenias that could emerge with longer follow-up. On the operational front, the ability to scale a 12-day autologous TCR-T workflow across multiple high-volume transplant centers will determine enrollment velocity. If survival trends persist with adequate event counts and the control framework holds up under regulatory review, the program could redefine post-transplant relapse prevention; if not, the field may revert to combination and donor-derived strategies with clearer randomization pathways. Watch for ASH follow-ons, a finalized pivotal synopsis, and early comparability data from the updated manufacturing run.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
