Clinical Development of Gamma-Delta T-Cell Therapy INB-400 Paused in Glioblastoma

Enrollment onto the phase 2 trial (NCT05664243) investigating the DeltEx gamma-delta T-cell therapy INB-400 in combination with temozolomide (Temodal) in patients with newly diagnosed glioblastoma multiforme (GBM) has been suspended, according to an announcement from IN8bio.¹

The company has announced that it will pause its GBM development program and explore potential partnership opportunities for its solid tumor drug development program. However, patients enrolled onto this study along with a phase 1 trial (NCT04165941) of INB-200 will continue to be monitored for long-term remissions and overall survival (OS).

IN8bio stated that this trial suspension is part of a plan to optimize resource allocation and focus on continuing to generate robust clinical data from an ongoing, investigator-sponsored phase 1 trial (NCT03533816) evaluating the gamma-delta T-cell therapy INB-100 following hematopoietic stem cell transplant and post-transplant cyclophosphamide in patients with hematologic malignancies, such as acute myeloid leukemia (AML).²

All patients in the phase 1 trial of INB-200 have completed treatment with a maximum of 6 repeat doses of DeltEx DRI gamma-delta T cells plus temozolomide.1 Further enrollment to the phase 2 trial of INB-400 will be paused as IN8bio explores potential partnership opportunities for their solid tumor drug development program.

“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,” William Ho, chief executive officer and co-founder of IN8bio, stated in a news release. “These are hard but necessary steps to enable us to continue developing these novel cellular immunotherapies that are demonstrating signs of clinical activity in difficult[-to-treat patients with] cancer. We are excited to focus on INB-100, as IN8bio and its investigators believe patient outcomes in its trial to date are surpassing that of similar [patients with] leukemia, including those with AML undergoing haploidentical transplantation without receiving INB-100.”

Phase 1 Trial of INB-200

Adult patients with newly diagnosed GBM, adequate organ function, and a Karnofsky performance score of at least 70% were enrolled onto the study.³ Patients received 1, 3, or 6 doses of DeltEx drug-resistant immunotherapy (DRI) at 1 x 107 DRI cells per dose plus 150 mg/m2 of intravenous temozolomide on day 1 of each Stupp maintenance cycle. Safety served as the primary end point; survival was a secondary end point.

In total, 23 patients were enrolled. Among the 13 patients who received treatment, 1 had a best response of progressive disease (PD), 11 had best responses of 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.

Among the treated patients, no DRI-related toxicities or dose-limiting toxicities were observed, 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. No treatment-related deaths occurred. Eight patients died due to PD or disease-related issues (n = 7) and an unrelated cardiac event (n = 1).

Phase 2 Trial of INB-400

This study 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%.⁴ In the phase 1b cohort, patients with relapsed disease received allogeneic DeltEx gamma-delta T-cell therapy with INB-400 plus temozolomide at 150 mg/m2 on day 1 of 6 28-day cycles. In phase 2 arm A, patients with newly diagnosed disease received autologous INB-400 on day 1 of 6 28-day cycles in combination with temozolomide maintenance therapy. In phase 2 arm B, patients with relapsed disease received allogeneic INB-400 plus temozolomide at 150 mg/m2 on day 1 of 6 28-day cycles. In phase 2 arm C, patients with newly diagnosed disease received allogeneic INB-400 in combination with temozolomide on day 1 of 6 28-day cycles in combination with temozolomide maintenance therapy.

The primary end point in the phase 1b portion was the establishment of the recommended phase 2 dose of INB-400. The primary end point in phase 2 arms A and C was 12-month OS rate. The primary end point in phase 2 arm B was 9-month OS rate. Secondary end points included safety, tolerability, overall response rate, time to progression, PFS, and definition of product characteristics.

References

1. IN8bio announces clinical pipeline prioritization to focus on INB-100 for acute myeloid leukemia. News release. IN8bio, Inc. September 4, 2024. Accessed September 10, 2024. https://investors.in8bio.com/news-releases/news-release-details/in8bio-announces-clinical-pipeline-prioritization-focus-inb-100
2. Expanded/activated gamma delta T-cell infusion following hematopoietic stem cell transplantation and post-transplant cyclophosphamide. ClinicalTrials.gov. Updated February 8, 2023. Accessed September 10, 2024. https://clinicaltrials.gov/study/NCT03533816
3. Lobbous M, Goswami T, Lamb LS, et al. INB-200: fully enrolled phase 1 study of gene-modified autologous gamma-delta (γδ) T cells in patients with newly diagnosed glioblastoma multiforme (GBM) receiving maintenance temozolomide (TMZ). J Clin Oncol. 2024;42(suppl 16):2042. doi:10.1200/JCO.2024.42.16_suppl.2042
4. A phase 1b/2 drug resistant immunotherapy with activated, gene modified allogeneic or autologous γδ T cells (DeltEx) in combination with maintenance temozolomide in subjects with recurrent or newly diagnosed glioblastoma. ClinicalTrials.gov. Updated July 11, 2024. Accessed August 10, 2024. https://clinicaltrials.gov/study/NCT05664243