INB-100 After HSCT Shows Enduring Efficacy in Complex Leukemias

Early INB-100 results showed the potential to achieve durable remissions and improve survival in patients with complex leukemias, particularly AML.

INB-100, an allogenic gamma-delta T-cell therapy, administered after hematopoietic stem cell transplantation (HSCT) elicited long-term efficacy in an investigator-sponsored phase 1 trial (NCT03533816) in the treatment of patients with complex leukemias, including acute myeloid leukemia (AML), according to a press release from the developer, IN8bio.¹

The treatment demonstrated the potential to improve survival and achieve durable long-term remissions. Results were shared in an investor presentation.² Full results are going to be presented at the 2025 Tandem Meetings.

In all patients, INB-100 yielded a progression-free survival (PFS) rate of 90.9% and an overall survival (OS) rate of 100% at 1 year. In patients with AML, PFS and OS were both 100% at 1 year with INB-100 vs rates of 67.8% and 74.7% for historical AML control cohorts, respectively, at the Center for International Blood and Marrow Transplant Research (CIBMTR) and 57.4% and 66.7%, respectively, at the Kansas University Cancer Center.

“These data suggest that the addition of allogeneic INB-100 gamma-delta T cells appears to have the potential to support durable relapse-free remissions in [patients with] high-risk leukemia, with 100% of treated [patients with] AML remaining in remission after a median follow-up of almost 2 years post-transplant,” Joseph P. McGuirk, DO, Schutte-Speas professor of Hematology-Oncology, division director, and medical director of Hematologic Malignancies and Cellular Therapeutics, Blood and Marrow Transplant, at The University of Kansas Cancer Center, stated in the release.¹ “These results are truly exciting. We are seeing something we rarely encounter in [patients with] high-risk leukemia: sustained, durable remissions with minimal [adverse] effects to date. These continued results of INB-100, with the manageable toxicity profile, suggest it could become an attractive cellular therapy with the potential to extend survival in this difficult-to-treat patient population.”

All patients with AML (n = 9) achieved a median duration of remission of 20.1 months. Patients with AML who were in the original cohort have reached a median complete remission of 23.3 months.

A total of 23 patients were enrolled in the trial, and 16 were fully dosed and evaluable for safety data; 1 patient was waiting to be dosed as of January 17, 2025.² The median age of patients was 68 years, the majority had AML, and patients received up to 7 prior therapies.

Treatment consisted of a reduced intensity conditioning regimen of fludarabine, cyclophosphamide, and total body irradiation, then haploidentical HSCT with neutrophil engraftment 15 to 20 days following HSCT, then INB-100 infusion within 7 days of engraftment. INB-100 was given at single doses of 1 x 10⁶ cells/kg, 3 x 10⁶ cells/kg, or 1 x 10⁷ cells/kg.

Eligible patients were adults with an identified haploidentical donor; a Karnofsky performance status of 70 or greater; and AML in molecular CR (mCR) with intermediate/high-risk features or relapsed disease, chronic myeloid leukemia in any chronic phase, myelodysplastic syndrome with intermediate/high-risk features, or acute lymphoblastic leukemia in mCR with high-risk features or relapsed disease.

The trial’s primary end points were safety, dose-limiting toxicity, and recommended phase 2 dose of DeltEx™ gamma-delta T cell infusion. Secondary end points were incidence of acute and chronic graft-versus-host disease, relapse, and OS.

Regarding safety, the most common treatment-emergent adverse events (TEAEs) of any grade were anemia (88.2%), platelet count decreases (82.4%), hypomagnesemia (70.6%), white blood cell decreases (58.8%), absolute neutrophil count decreases (58.8%), and creatinine increases (52.9%). Of grade 4 toxicities, the most common TEAEs were platelet count decreases (52.9%), absolute neutrophil count decreases (35.3%), white blood cell decreases (23.5%), and absolute lymphocyte count decreases (11.8%). Potential treatment-related serious AEs were grade 2/3 maculopapular rash, grade 3 nausea, and grade 3 anemia.

At a data-cutoff of January 17, 2025, there were no treatment-related dose-limiting toxicities, no suspected unexpected serious adverse reactions, and no treatment-related deaths.

References

1. IN8bio reports updated positive results from phase 1 trial of INB-100 in leukemia patients. News release. IN8bio, Inc. February 11, 2025. Accessed February 12, 2025. https://tinyurl.com/yeyr3prt
2. Harnessing the Power of Gamma-Delta T Cells. IN8bio. February 11, 2025. https://tinyurl.com/mw62by6z