IN8bio has announced the suspension of enrollment in its phase 2 clinical trial investigating INB-400, a DeltEx gamma-delta T-cell therapy, in combination with temozolomide for patients with newly diagnosed glioblastoma multiforme (GBM). This decision marks a shift in the company's strategic priorities, with a greater emphasis now placed on its INB-100 program for acute myeloid leukemia (AML).
The company plans to explore potential partnership opportunities for its solid tumor drug development program. However, patients currently enrolled in the INB-400 trial (NCT05664243), along with those in the phase 1 trial of INB-200 (NCT04165941), will continue to be monitored for long-term remissions and overall survival (OS).
Strategic Shift to Prioritize AML Program
According to IN8bio, the trial suspension is part of a broader plan to optimize resource allocation and concentrate on generating robust clinical data from an ongoing, investigator-sponsored phase 1 trial (NCT03533816) evaluating INB-100. This therapy involves gamma-delta T-cell infusion following hematopoietic stem cell transplant and post-transplant cyclophosphamide in patients with hematologic malignancies, particularly AML.
William Ho, CEO of IN8bio, stated, "The data across both of our INB-100 and INB-200 clinical programs remain positive and robust. We are committed to building upon the data for INB-100 in AML, and we are making the difficult decision to advance fewer pipeline programs, reduce our spending, and focus on key milestones that can help to generate near-term interest and value creation."
INB-200 Phase 1 Trial Data
The phase 1 trial of INB-200 enrolled adult patients with newly diagnosed GBM who had adequate organ function and a Karnofsky performance score of at least 70%. Patients received 1, 3, or 6 doses of DeltEx drug-resistant immunotherapy (DRI) at 1 x 107 DRI cells per dose, along with 150 mg/m2 of intravenous temozolomide on day 1 of each Stupp maintenance cycle. The primary endpoint was safety, with survival as a secondary endpoint.
In total, 23 patients were enrolled, and among the 13 patients who received treatment, 1 had progressive disease (PD), 11 had stable disease, and 1 was not evaluable for response. At a median follow-up of 10.8 months, the median progression-free survival (PFS) was 7 months. Five patients remain in follow-up.
Notably, no DRI-related toxicities or dose-limiting toxicities were observed among the treated patients, and no patients developed cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome. Most toxicities were grade 1/2 and were attributed to temozolomide. There were no treatment-related deaths; however, eight patients died due to PD or disease-related issues (n = 7) and an unrelated cardiac event (n = 1).
INB-400 Phase 2 Trial Design
The phase 2 trial of INB-400 enrolled patients at least 18 years of age with a histologically or cytologically confirmed history of IDH wild-type glioblastoma and a Karnofsky performance score of at least 70%. The trial included multiple arms to evaluate different treatment approaches.
In the phase 1b cohort, patients with relapsed disease received allogeneic DeltEx gamma-delta T-cell therapy with INB-400 plus temozolomide. Phase 2 arm A involved patients with newly diagnosed disease receiving autologous INB-400 in combination with temozolomide maintenance therapy. Phase 2 arm B included patients with relapsed disease receiving allogeneic INB-400 plus temozolomide. Phase 2 arm C involved patients with newly diagnosed disease receiving allogeneic INB-400 in combination with temozolomide maintenance therapy.
The primary endpoint in the phase 1b portion was establishing the recommended phase 2 dose of INB-400. The primary endpoint in phase 2 arms A and C was the 12-month OS rate, while in phase 2 arm B, it was the 9-month OS rate. Secondary endpoints included safety, tolerability, overall response rate, time to progression, PFS, and definition of product characteristics.
