The novel therapy INB-200 in combination with concomitant temozolomide may improve survival in patients with glioblastoma multiforme, according to preliminary findings from a phase I clinical trial presented by Lobbous et al at the 2024 ASCO Annual Meeting (Abstract 2042).
“For far too long, there has been little advancement for patients with glioblastoma multiforme to improve their treatment outcomes,” stressed senior study author Burt Nabors, MD, Professor of Neurology, Director of the Division of Neuro-Oncology, and a senior scientist at the O’Neal Comprehensive Cancer Center at the University of Alabama at Birmingham.
The current standard of care in patients with newly diagnosed glioma consists of primary resection and 6 weeks of daily chemoradiation therapy followed by six cycles of monthly temozolomide maintenance therapy. Known as the Stupp regimen, this protocol typically achieves a median progression-free survival of 7 months and an overall survival of about 14 to 16 months.
INB-200 is a treatment that involves genetically modified, autologous, chemotherapy-resistant gamma-delta T cells—which are a specialized population of T cells capable of differentiating between healthy and diseased tissue.
Study Methods and Results
In the new clinical trial, the researchers assessed the safety and preliminary efficacy of INB-200 in addition to temozolomide maintenance therapy in 13 patients with glioblastoma multiforme. A total of 23 patients were enrolled in the trial. The researchers administered 10 million cells per dose across three different dosing regimens: a single dose delivered on day 1 of cycle 1 during maintenance therapy in cohort 1 (n = 3), three doses delivered on day of cycles 1 to 3 in cohort 2 (n = 4), and six doses delivered on day 1 of cycles 1 to 6 in cohort 3 (n = 6).
After a median follow-up of 11.7 months, the researchers found that 92% of the evaluable patients who received INB-200 plus temozolomide chemotherapy exceeded the median progression-free survival of 7 months. All of the patients who received all of their protocol-defined treatments with INB-200 exceeded the median progression-free survival, including one patient in cohort 2 who is currently alive and progression free after nearly 3 years.
Radiographic evaluation pre- and posttreatment included resolution of midline shift in one patient, with evidence of changes in enhancement attributed to treatment effects in multiple patients. The researchers noted that one of the patients had a 36% decrease in a lesion, attributed to positive treatment effects.
The researchers reported no treatment-related serious adverse events in any of the cohorts.
“The safety profile of gamma-delta T cells continues to be strong across all three dose cohorts with no cell therapy–related toxicities such as immune effector cell–associated neurotoxicity syndrome or cytokine-release syndrome reported in patients receiving up to the maximum dose of six infusions of the therapy,” highlighted co–study author Trishna Goswami, MD, Chief Medical Officer at IN8bio.
Conclusions
“The addition of multiple intracranial injections of … gamma-delta T cells shows the potential for extending progression-free survival in this patient population when administered in combination with the current standard of care used to treat newly diagnosed glioblastoma,” emphasized Dr. Nabors.
The researchers indicated that the new findings alongside radiographic improvements may demonstrate the potential of INB-200 to become a first-in-class therapy in patients with newly diagnosed glioblastoma.
“We are now dosing newly diagnosed patients in arm A of a phase II study with INB-400, evaluating up to six infusions of … autologous gamma-delta T cells in combination with the Stupp protocol,” Dr. Goswami detailed.
“As these encouraging results from our ongoing … phase I study continue to mature, we look forward to reporting additional results from a long-term follow-up of cohort 3 at future medical meetings,” concluded William Ho, MBA, Chief Executive Officer and co-founder of IN8bio.
Disclosure: For full disclosures of the study authors, visit meetings.asco.org.
