TScan Therapeutics reported positive Phase 1 ALLOHA™ data for TSC-101, with 11 of 14 patients achieving complete donor chimerism within weeks of treatment, supporting the launch of a pivotal Phase 3 study in hematologic malignancies.
Written By: Shaik Yasmeen, PharmD
Reviewed By: Pharmacally Editorial Team
TScan Therapeutics has reported promising early results from Cohort C of its ongoing ALLOHA™ Phase 1 study (NCT05473910) evaluating TSC-101, a T-cell receptor-engineered therapy intended to reduce relapse risk following allogeneic hematopoietic cell transplantation (allo-HCT) in patients with hematologic malignancies.
The latest findings showed that 11 of 14 treated patients achieved complete donor chimerism within approximately three weeks after their first TSC-101 infusion. Two additional patients demonstrated continued improvement toward complete donor chimerism, while all five evaluable patients assessed after a second infusion achieved complete donor chimerism. The results support the company’s plan to initiate the pivotal Phase 3 ALLOHA-2™ study later this month.
Understanding TSC-101 and the Clinical Need
Despite advances in stem cell transplantation, disease relapse remains one of the leading causes of death after allo-HCT in patients with leukemia and other blood cancers. Residual recipient immune cells that persist after transplant can contribute to relapse risk and undermine long-term treatment success.
TSC-101 is an engineered T-cell receptor (TCR-T) therapy developed to selectively eliminate recipient cells that remain after transplantation. By promoting complete donor chimerism, the therapy aims to enhance donor immune system engraftment and reduce the likelihood of disease recurrence.
Cohort C Results Validate Commercial-Ready Manufacturing Process
Cohort C evaluated TSC-101 produced using TScan’s commercial-ready manufacturing process. Nineteen patients were enrolled, and manufacturing was successful in 17 patients, representing an approximately 90% manufacturing success rate.
Among enrolled participants, 14 proceeded to transplant and received a first TSC-101 infusion. Ten patients subsequently received their planned second infusion, while one patient received a third infusion. Three patients did not undergo transplant because of clinical factors unrelated to manufacturing.
Using a high-sensitivity next-generation sequencing assay to assess donor chimerism, investigators observed complete donor chimerism in 11 of 14 patients within roughly three weeks of the first infusion. Two additional patients continued to show declining recipient chimerism and were approaching complete donor chimerism. Notably, one patient with TP53-mutated acute myeloid leukemia maintained complete donor chimerism six months after transplantation.
Safety Remains Consistent
TSC-101 continued to demonstrate a favorable tolerability profile. Investigators reported that treatment-related safety findings were consistent with earlier Cohort A observations, and adverse events largely reflected expected complications commonly seen following allo-HCT.
The combination of rapid donor chimerism conversion and a manageable safety profile strengthens confidence in the therapeutic approach as the program advances into late-stage development.
Clinical Leadership Viewpoint
Chief Executive Officer Gavin MacBeath noted that the data reinforce confidence in both the product’s clinical activity and the consistency of the commercial-ready manufacturing process. He highlighted that 93% of evaluable patients experienced decreasing recipient chimerism despite representing a higher-risk population than those enrolled in earlier cohorts.
Chief Medical Officer Chrystal Louis emphasized the persistent unmet need following allo-HCT, where relapse remains a major challenge despite curative intent treatment. She noted that strong investigator participation and ahead-of-schedule enrollment reflect growing interest in the program.
With Cohort C meeting key clinical and manufacturing objectives, TScan is preparing to launch the pivotal Phase 3 ALLOHA-2 study, which will further evaluate whether TSC-101 can reduce relapse risk and improve long-term outcomes for patients undergoing stem cell transplantation for hematologic cancers.
What This Means for Patients
For patients with leukemia and other blood cancers undergoing stem cell transplantation, relapse remains a major threat even after potentially curative treatment. The early TSC-101 results suggest that strengthening donor immune system engraftment soon after transplant may help eliminate residual cancer cells and lower the risk of disease recurrence. If confirmed in Phase 3 studies, TSC-101 could become a new post-transplant treatment option that improves long-term survival and transplant outcomes.
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About the Writer
Shaik Yasmeen (LinkedIn) is a Pharm.D graduate with interests in clinical pharmacy, pharmacovigilance, and medical writing. She has gained experience through hospital clinical postings, patient case reviews, case presentations, and literature evaluation. Passionate about evidence-based healthcare, she is committed to creating accurate and engaging medical content while continuously expanding her professional knowledge.