Updated results from the ongoing ALLOHA™ Phase 1 trial (NCT05473910) of TSC-101, an investigational T cell receptor (TCR) engineered T-cell (TCR-T) therapy being developed by TScan Therapeutics for the treatment of patients with hematological malignancies undergoing allogeneic hematopoietic cell transplantation (HCT) were featured in a poster presentation at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition beiging held December 6 – 9, 2025 in Orlando, Florida.
The investigational agent targets the minor histocompatibility antigen HA-2 in HLA-A*02:01-positive patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or myelodysplastic syndrome (MDS) who are receiving reduced-intensity conditioning (RIC) haploidentical HCT to eliminate residual disease, thereby reducing relapse rates and promoting complete donor chimerism.
Patients in the treatment arm received TSC-101 after standard-of-care HCT, whereas control-arm patients received standard-of-care HCT alone.
The study results showed favorable relapse-free survival (HR=0.50; p=0.23) and overall survival (HR=0.61; p=0.52). All participating patients treated with TSC-101 who reached two-year follow-up remained relapse-free, compared with 25% of patients in the control arm. The trial results also demonstrated that TSC-101 was well tolerated, with no dose-limiting toxicities observed.
“These updated data from our Phase 1 study continue to highlight a positive safety and efficacy profile of TSC-101 in patients with heme malignancies undergoing allogeneic HCT. All three patients who reached two years of follow-up have no detectable disease as they have remained relapse-free and in complete donor chimerism,” explained Chrystal U. Louis, M.D., Chief Medical Officer.
“Additionally, there have been no dose-limiting toxicities (DLT), and patients who received TSC-101 continue to show improved relapse-free and overall survival compared to control-arm patients. We remain focused on enrolling the remaining patients necessary to support our fixed-dosing regimen and look forward to initiating our pivotal study in the second quarter of 2026,” Louis added.
Unmet medical need
“Bone marrow transplantation is currently the only curative treatment for patients with AML and MDS. Unfortunately, roughly 40% of these patients relapse within two years of transplant, at which point their prognosis is very poor, and the majority will die due to their disease,” added Gavin MacBeath, Ph.D., Chief Executive Officer.
“We are excited to see durable responses to TSC-101 and continued positive data, in the hopes of addressing this unmet need. We look forward to expanding our heme program in 2026 with product candidates designed to double the addressable patient population.”
Study Highlights
- Relapse-free survival (RFS) (HR=0.50; p=0.23) and overall survival (OS) (HR=0.61; p=0.52) were improved in the treatment arm relative to the control arm.
- 4 of 19 (21%) treatment-arm patients relapsed compared to 6 of 18 (33%) control-arm patients.
- One treatment-arm patient with AML experienced disease relapse on day 161 and was given a third dose of TSC-101 without lymphodepletion. The additional administration of TSC-101 resulted in a complete response, including complete donor chimerism, that was maintained for 5 months.
- The hazard ratio for the probability of relapse was 0.46 (p=0.22).
- 8 of 37 (22%) patients had TP53 mutations, with 6 cases in the treatment arm and 2 cases in the control arm. Of the 6 patients in the treatment arm, only 1 has relapsed. Both patients with TP53 mutations in the control arm have relapsed and subsequently succumbed to their disease. The first patient with a TP53 mutation to receive TSC-101 has now reached two years of follow-up and remains relapse-free.
- 4 of 19 (21%) treatment-arm patients relapsed compared to 6 of 18 (33%) control-arm patients.
- All 3 (100%) TSC-101-treated patients who reached 2 years of follow-up remained relapse-free as of the data cutoff, compared with 1 of 4 (25%) patients in the control arm, consistent with effective elimination of residual cancer cells post-HCT and durable remission with TSC-101 infusion.
- TSC-101 infusions were well tolerated across all dose levels, with no dose-limiting toxicities. Observed adverse events were similar across the treatment and control arms and were generally consistent with post-HCT adverse events.
- Mixed chimerism or relapses following TSC-101 infusions were significantly associated with greater ex vivo expansion of TCR-T cells during manufacturing. A new commercial-ready process reduces the manufacturing time from 17 days to 12 days and has a significant reduction in ex vivo
The Company recently announced that the U.S. Food and Drug Administration (FDA) has agreed to a pivotal study design for TSC-101 that mirrors the current ALLOHA™ Phase 1 trial using a biologically assigned internal control arm.
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Clinical trials
A Study of TSC-100 and TSC-101 in AML, ALL, and MDS in Patients Undergoing Allogeneic Peripheral Blood Stem Transplantation – ClinicalTrials.gov ID NCT05473910
Reference
Al Malki M, Chen YB, Jain T, Keyzner A, Solh M, Popat U, Donato M, Pineiro L, Fernandez H, Gill S, Snow A, Uberti J, White T, Wang Y, Nguyen C, Louis CU, Chattopadhyay S, Matzko M, Reshef R. TSC-101 eliminates recipient hematopoietic cells and demonstrates potential for improved relapse-free survival in patients with AML, ALL, or MDS undergoing allogeneic HCT: Updated results from the Phase 1 (ALLOHA) trial. 67th ASH® / American Society of Hematology Annual Meeting. [Abstract 12098]
Featured image: New Orleans, LA – ASH – Photo courtesy © 2022 ASH/Nick Agro. Used with permission.
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