IN8bio’s Gamma-Delta T-cell Therapy INB-100 Helps Maintain Complete Remissions After HSCT in Patients With Hematologic Malignancies

Patients with hematologic malignancies treated with IN8bio’s INB-100, an allogeneic gamma-delta T-cell therapy, after receiving haploidentical stem cell transplant (HSCT) have maintained complete remissions (CRs) for over a year.¹ The data, which comes from a phase 1 clinical trial (NCT03533816), were presented in a poster at the European Hematology Association (EHA) 2024 Congress, held June 13 to 16, both virtually and in Madrid, Spain.

Among 10 patients who were treated with INB-100 in the trial, all 10 (100%) maintained their state of CR at 12 months or more posttreatment, with a median follow-up time of 17.4 months. It was additionally noted that 3 patients who have high-risk disease have remained free of relapse for more than 35 months. First author Joseph P. McGuirk, MD, the Schutte-Speas professor of hematology-oncology, division director, hematologic malignancies and cellular therapeutics medical director, blood and marrow transplant, at the University of Kansas Cancer Center, and colleagues also pointed out that the study is the first to have shown in vivo expansion and persistence of gamma-delta T-cells for up to a year after HSCT.

“This data demonstrates the potential of allogeneic INB-100 gamma-delta T-cells to provide durable relapse-free periods for high-risk or relapsed acute myeloid leukemia (AML) and other hematologic malignancies undergoing HSCT,” Trishna Goswami, MD, the chief medical officer of IN8bio, said in a statement.² “100% of evaluable patients remain in complete remission at one year of follow-up. In this trial, the first three patients were high-risk or relapsed AML patients with complex cytogenetics, including trisomy of chromosome 8 and deletion of chromosome 7. All 3 patients remain alive and progression free with one lost-to-follow-up at 42.4 months after they relocated away from the study site. Achieving these outcomes despite giving patients a reduced intensity conditioning regimen, which carries a higher risk of relapse, in an older population with a median age of 68 is very encouraging. We look forward to advancing our novel gamma-delta T cell therapy for patients who need additional options.”

In terms of safety, there were no dose-limiting toxicities and no cases of cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome (ICANS) reported.² Although, 2 patients did experience cases of cytomegalovirus (CMV) reactivation. Furthermore, one patient experienced a chronic extensive case of graft versus host disease (GvHD) and 2 patients experienced cases of chronic limited GvHD. All cases of acute GvHD (aGvHD) were grade 2 or lower.

Serious adverse events (SAEs) deemed related to treatment included a grade 2 case of rash maculopapular and a grade 3 case of nausea (aGvHD 2B GI). SAEs deemed unrelated to treatment included grade 3 cases of acute kidney injury, anemia, CMV reactivation, fall, and decreased appetite. McGuirk and colleagues noted that infection rates were low, there were no unexpected safety results, and that the AE profile did not differ between dose-level 1 (DL1) and dose-level 2 (DL2).

One patient in the study passed away after treatment with INB-100, but the death was not deemed related to INB-100.The patient’s death was attributed to idiopathic pulmonary fibrosis, which IN8bio noted is a known toxicity caused by transplants.² The patient did not show evidence of disease progression. Two other patients treated with INB-100 experienced disease relapse, one after 12.5 months in CR and the other after 14.7 months in CR.¹ These 2 patients, who the company noted both have TP53 mutations, are still living.²

“The emerging safety, efficacy and durability profile of this novel gamma-delta T cell therapy supports its potential to improve relapse-free survival for patients with blood cancers following allogeneic stem cell transplantation,” McGuirk added to the statement.² “Approximately 25% of patients relapse within the first 100 days, and nearly half by 1 year post stem cell transplant, which remains the primary cause of treatment failure and mortality. The results of this clinical trial are very encouraging and hold promise that a novel cellular therapy using donor-derived gamma-delta T cells may prevent relapse, resulting in improved relapse-free survival for patients with hematologic malignancies.”

The trial enrolled 14 patients in total, but 1 patient died before receiving INB-100, another patient was treated with an out of specification dose of INB-100, a third patient’s dose was not successfully manufactured, and a fourth patient did not pass screening because their disease relapsed before treatment.¹ Four of the 10 succesfully treated patients received INB-100 at DL1 (1x10⁶ cells/kg) and the other 6 patients received INB-100 at DL2 (3x10⁶ cells/kg). Eight of the treated patients had AML, 1 had acute lymphoblastic leukemia, and 1 had myelodysplastic/myeloproliferative neoplasms. The treatment group included 6 men and 4 women; ages ranged from 44 to 71 years.

In light of the promising results, IN8bio is working on expanding the DL2 cohort to include 10 additional patients. The company is also planning a confirmatory study.

REFERENCES
1. McGuirk J, Abhyankar S, Goswami T, et al. 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: the European Hematology Association (EHA) 2024Hybrid Congress, June 13-16, held both virtually and in Madrid, Spain. Abstract #P1460
2. IN8bio presents durable complete remission in 100% of evaluable patients in phase 1 inb-100 trial in leukemia at European Hematology Association 2024. News release. June 13, 2024. Accessed June 13, 2024. https://investors.in8bio.com/news-releases/news-release-details/in8bio-presents-positive-data-demonstrating-durable-1-year