INB-100 Following HSCT Displays Long-Lasting Activity in Pretreated AML

Treatment with the allogeneic γδ T-cell therapy INB-100 after hematopoietic stem cell transplantation (HSCT) led to durable remissions and extended survival in patients with pretreated acute myeloid leukemia (AML), according to findings from a phase 1 study (NCT03533816) presented during the 2025 Transplant and Cellular Therapy Meetings.1,2

At a median follow-up of 20.1 months (23.3 months, ex-expansion cohort), all efficacy-evaluable patients with AML (n = 9) in the original and expansion cohorts remained in complete remission (CR) as of the January 17, 2025, data cutoff.1,2 The 1-year progression-free survival (PFS) and overall survival (OS) rates were both 100%. Notably, 3 patients with high-risk disease remained relapse free for over 3 years.2

Additional findings from the study showed that, at a median follow-up of 18.8 months, all efficacy-evaluable patients with hematologic cancers who received INB-100 (n = 11) achieved a 1-year PFS rate of 90.9%. The 1-year OS rate was 100%.

“These data suggest that the addition of allogeneic INB-100 γδ T cells appears to have the potential to support durable relapse-free remissions in high-risk leukemia patients, with 100% of treated AML patients remaining in remission after a median follow-up of almost 2 years post-transplant,” Joseph P. McGuirk, DO, stated in a news release.1 “Typically, patients receiving reduced-intensity conditioning face substantial risks of relapse within a year, and those who relapse are often left with very few treatment options. INB-100 is not only helping patients avoid this common relapse timeline but is doing so while helping to preserve their quality of life.”

McGuirk, who was also the first study author of the poster presented at the meeting, is the Schutte-Speas Professor of Hematologic Malignancies and Cellular Therapeutics at The University of Kansas Medical Center in Kansas City.

The phase 1 study enrolled adult patients with an identified haploidentical HSCT donor and a Karnofsky Performance Status score of at least 70.2 Eligible patients needed to have AML in morphologic CR with intermediate- or high-risk features or relapsed disease, chronic myeloid leukemia in any chronic phase, myelodysplastic syndrome (MDS) with intermediate- or high-risk features, or acute lymphoblastic leukemia with high-risk features or relapsed disease.

After enrollment, patients received fludarabine plus cyclophosphamide and total body irradiation for 6 days followed by haploidentical HSCT. Within 7 days of neutrophil engraftment, which occurred approximately 15 to 20 days after HSCT, patients received a single dose of INB-100. INB-100 was administered at 1 x 106 cells/kg or the recommended phase 2 dose (RP2D) of 3 x 106m cells/kg.

The primary end points were safety, determining the RP2D of INB-100, and the incidence of dose-limiting toxicities (DLTs). Secondary end points included the incidence of acute and chronic graft vs host disease, relapse rate, and OS.

At baseline, the median age across all patients was approximately 68 years. Patients received up to 7 prior lines of treatment, and among the 23 enrolled in the study, 16 received a dose of INB-100.

In the safety population (n = 17), no treatment-related deaths or DLTs were reported at the data cutoff. Any-grade treatment-emergent adverse effects (TEAEs) included anemia (88.2%), decreased platelet counts (82.4%), and hypomagnesemia (70.6%). Common grade 3 TEAEs included anemia (70.6%) and decreased absolute lymphocyte count (23.5%). Furthermore, grade 4 TEAEs that occurred were decreased platelet counts (52.9%), decreased absolute neutrophil counts (35.3%), decreased white blood cell counts (23.5%), and decreased absolute lymphocyte count (11.8%).

“These results are truly exciting. We are seeing something we rarely encounter in [patients with] high-risk leukemia: sustained, durable remissions with minimal [AEs] to date,” McGuirk said in the news release.1 “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.”

The study authors also noted that this was the first trial to show in vivo expansion and persistence of γδ T cells for 1 year after HSCT which indicated that elevated γδ T cells and continued immune surveillance could be driving the longer PFS.2 A 15-patient expansion cohort is enrolling patients to receive the RP2D of INB-100 and there is potential for a future randomized controlled trial of patients with AML.

“As we continue to enroll patients and expand the trial network, we are working diligently to lay the groundwork for the future regulatory pathway towards a potential registrational trial. The IN8bio team is working hard to derisk the future path to approval and to bring this innovative therapy towards broader patient access. We are committed to providing further updates later this year as we build momentum toward this goal,” William Ho, chief executive officer and cofounder of IN8bio added in the news release.1

References

1. IN8bio reports updated positive results from phase 1 trial of INB-100 in leukemia patients. News release. IN8bio. February 11, 2025. Accessed March 3, 2025. https://www.globenewswire.com/news-release/2025/02/11/3024098/0/en/IN8bio-Reports-Updated-Positive-Results-from-Phase-1-Trial-of-INB-100-in-Leukemia-Patients.html
2. McGuirk JP, Abhyankar SH, ter Haak M, Chen G, Rochlin K, Lamb LS. Inb-100: pilot study of donor derived, ex-vivo expanded/activated gamma-delta t cell infusion following haploidentical hematopoietic stem-cell transplantation and post-transplant cyclophosphamide. Presented at: 2025 Transplant and Cellular Therapy Meetings; February 12-15, 2025; Honolulu, HI. Abstract 291.