Promising Phase 1 data for glioblastoma treatment

Preliminary findings from a Phase 1 clinical trial for glioblastoma multiforme patients have shown promising results for a new treatment involving the drug INB-200. Conducted at the University of Alabama at Birmingham (UAB), the trial revealed that 92 percent of evaluable patients treated with INB-200 surpassed a median progression-free survival of seven months while undergoing concomitant temozolomide chemotherapy. The median follow-up period was 11.7 months. These results, accompanied by radiographic improvements, suggest a positive response to the treatment, highlighting the potential of IN8bio's genetically modified, chemotherapy-resistant gamma-delta T cells as a novel therapy for newly diagnosed glioblastoma patients.

Led by Burt Nabors, M.D., a prominent professor of neurology at UAB and division director of Neuro-Oncology, the trial was a collaborative effort with IN8bio. Dr. Larry Lamb, a former UAB professor and the scientific co-founder and current chief scientific officer at IN8bio, played a crucial role in developing this innovative technology. INB-200 marks the first genetically modified gamma-delta T cell therapy to enter clinical trials, with its intellectual property licensed through UAB's Bill L. Harbert Institute for Innovation and Entrepreneurship.

The standard treatment for newly diagnosed glioma patients typically involves primary resection followed by six weeks of daily chemoradiation therapy and six cycles of monthly maintenance temozolomide therapy, known as the Stupp regimen. This protocol generally achieves a median progression-free survival of seven months and an overall survival ranging between 14 to 16 months. However, the new Phase 1 study aimed to explore the safety and preliminary efficacy of integrating DeltEx DRI gamma-delta T cells with the maintenance temozolomide therapy.

The study administered different dosages of 10 million cells per dose across three dosing regimens. Cohort 1 received a single dose on Day 1 of Cycle 1, Cohort 2 received three doses on Days 1 of Cycles 1-3, and Cohort 3 received six doses on Days 1 of Cycles 1-6. A total of thirteen patients participated, including three in Cohort 1, four in Cohort 2, and six in Cohort 3. Impressively, all patients who completed the protocol-defined treatments with INB-200 exceeded the median progression-free survival of seven months. Notably, one patient in Cohort 2 has remained alive and progression-free for nearly three years.

Dr. Nabors expressed optimism about the results, indicating that the addition of IN8bio's DeltEx DRI gamma-delta T cells could potentially extend progression-free survival when combined with the current standard care for glioblastoma patients. No treatment-related serious adverse events were reported, and the safety profile of gamma-delta T cells remained robust across all three dosage cohorts. There were no incidents of cell therapy-related toxicities such as immune effector cell-associated neurotoxicity syndrome or cytokine release syndrome.

Dr. Trishna Goswami, chief medical officer for IN8bio, confirmed the favorable safety profile and mentioned that newly diagnosed patients are now being treated in Arm A of a Phase 2 study with INB-400. This study evaluates up to six infusions of autologous gamma-delta T cells in combination with the Stupp protocol.

Radiographic evaluations before and after treatment showed significant improvements. For instance, one patient experienced a resolution of midline shift, and there were changes in enhancement attributed to the treatment effect in multiple patients. One subject even showed a 36 percent decrease in a lesion, suggesting a positive treatment effect. William Ho, CEO and co-founder of IN8bio, shared enthusiasm for the ongoing positive results and looks forward to presenting additional data from the long-term follow-up of Cohort 3 at future medical conferences.

These encouraging preliminary results were presented at the 2024 American Society of Clinical Oncology Annual Meeting in Chicago, with Dr. Mina Lobbous, an assistant professor of neurology at the Cleveland Clinic, serving as the poster presenter.