TCR-T Therapy Cleared for AML Trial in Combination With AlloHSCT


BSB-1001 targets HA-1 miHA and will be evaluated in the 1 phase 1/2a TCX-101 trial.

The FDA has cleared BlueSphere Bio’s investigational new drug (IND) application for the company’s T-cell receptor T-cell (TCR-T) therapy BSB-1001, allowing the company to open the forthcoming phase 1/2a TCX-101 trial in patients with high risk refractory acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and myeloid dysplastic syndrome (MDS), in conjunction with allogeneic hematopoietic stem cell transplantation (alloHSCT).1

“We are eager to begin treating patients in our TCX-101 trial,” Keir Loiacono, Esq, Chief Executive Officer,BlueSphere, said in a statement.1 “Our team is focused on accelerated identification, development and translation of novel products to the clinic. While alloHSCTprovides a chance of a cure for patients, a large fraction of patients will still relapse or do not have it as an option because of active leukemia. Deploying a TCR-based approach to blood restricted antigens - like miHAs combined with alloHSCT - could provide new options for these patients. We believe that BlueSphere’s unique approach to product and trial design will, among other things, enable us to treat patients who previously were unable to receive alloHSCT because of the presence of active leukemia.”

BlueSphere expects to enroll the first patient in the study in the fourth quarter of 2024. The study seeks to enroll patients with active morphologic disease or cytogenetic features placing them at high risk of relapse to receive simultaneous administration of BSB-1001 with allogeneic hematopoietic stem cell transplant (alloHSCT) without the use of immunosuppressive drugs.

BSB-1001 targets HA-1, a blood-restricted minor histocompatibility antigen (miHA) and was developed with BlueSphere’s TCXpress TCR identification and screening platform. The company’s second TCR-T candidate, designed to target NPM1, is currently in IND-enabling studies with a target filing date in the second quarter of 2025. The product will be autologous and not given in combination with alloHSCT.

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“The NPM1 mutation is a founder mutation present in approximately 30% of AML patients and is present throughout the duration of the disease, making it an ideal target for TCR-based therapy,” ErkutBahceci, MD, Chief Medical Officer, BlueSphere, added.1 “The advancement of the TCX-102 program in patients with mutant NPM1 demonstrates our commitment to this disease space and underscores the power of our TCR discovery platform to discover rare and potent TCR candidates.”

Recently, at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 31 to June 4, in Chicago, Illinois, Orca Bio presented data from a subgroup analysis of patients with AML treated with its lead candidate Orca-T, an investigational alternative to alloHSCT. The product consists of CD34+ stem cells, regulatory T-cells, and conventional T-cells from the peripheral blood of matched donors, designed to reduce the risk of graft versus host disease.2

“These new findings presented at ASCO show that Orca-T has the potential to offer curative therapy for patients with AML with very low rates—and in this case 0%—treatment-related mortality... In doing so, we're keeping the balance of graft versus leukemia—meaning not seeing higher rates of relapse—while still decreasing the risk of toxicities that we typically observe in an SOC stem cell transplantation. This approach hopefully has the potential to expand curative treatment to many more patients,” presenter Rawan Faramand, MD, assistant member, bone marrow transplant and Cellular Therapy, Moffit Cancer Center, told CGTLive®.

1. BlueSphere Bio Announces IND Clearance of its First in Human Candidate and New Cell Therapy Portfolio for High-Risk Leukemia Patients. News release. BlueSphere Bio. June 3, 2024.
2. Pantin JM, Patel SS, FaramandR, et al. Treatment of acute myeloid leukemia with Orca-T. Presented at: 2024 (ASCO) Annual Meeting; May 31-June 4; Chicago, Illinois.
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