TMZ γδ T-Cell Regimen May Have Potential in Treating Glioblastoma
A phase 1 trial evaluating INB-200 has shown a PFS benefit in treated participants.
Drug Resistance Immunotherapy (DRI) combining a standard regimen of temozolomide (TMZ) concomitantly with simultaneous intracranial infusion of TMZ-resistant γδ T-cells may be a potential treatment for glioblastoma (GBM). A publication in Frontiers in Immunology explored the approach, current strategy, and future directions for the therapeutic regimen.
INB200 is IN8bio’s autologous lead DRI candidate and is being evaluated in a first-in-human phase 1 clinical trial (NCT04165941) in participants with GBM.1 Another DRI candidate of IN8bio’s, INB-400, is also being evaluated in a phase 2 trial for newly diagnosed GBM.
“We believe our results to date represent a significant advancement in the treatment of GBM. By combining standard chemotherapy with gamma-delta T cells genetically engineered to resist the lymphodepleting effects of chemotherapy, we are creating a synergistic effect that enhances the immune response against GBM while minimizing toxicity to healthy tissues,” Lawrence Lamb, PhD, chief scientific officer and cofounder, IN8bio, said in a statement.2 “This new treatment may improve the survival and quality of life of patients with GBM by preventing tumor recurrence and enhancing the immune response to eliminate residual cancer cells.”
The current standard of care (SOC) for newly diagnosed GBM usually yields a median progression-free survival of 6 to 7 months and an overall survival of 14 to 16 months. The SOC typically involves primary tumor resection, 6 weeks of chemoradiation therapy, and 6 cycles of monthly maintenance therapy with TMZ.
READ MORE: Gamma-Delta T-cell Therapy Gets Green Light From FDA for Phase 2 Trial
The first-in-human trial is assessing the safety and efficacy of intracranial infusions of INB-200 in addition to SOC maintenance therapy in 3 different dosing regimens. Cohort 1 is receiving a single dose of 1x107 cells; cohort 2 is receiving 3 doses, on day 1 of cycles 1 to 3; and cohort 3 is receiving 6 doses, on day 1 of cycles 1 to 6.
The trial had an anticipated completion of enrollment by the end of 2023; interim findings for 15 enrolled participants were presented at the 2023 American Society of Clinical Oncology Meeting in June. The participants were 53% male, with a median age of 69 years (range, 21-76) and 8 had been treated as of the data cutoff date. Three were treated in cohort 1, 4 in cohort 2, and 1 in cohort 3. These patients have all exceeded the median PFS expected with SOC therapy alone. There have been no treatment-related serious adverse events, dose-limiting toxicities, cytokine release syndrome, infusion reactions, or immune effector cell-associated neurotoxicity syndrome.3
“The standard-of-care for GBM over the past twenty years falls short, with a median progression-free survival of just 4 to 7 months and overall survival of only 14 to 16 months. We are thrilled to see that two patients who have received three doses of INB-200 remain progression-free, clinically asymptomatic and off treatment for a prolonged period of time,” Trishna Goswami, MD, Chief Medical Officer, IN8bio, said in a statement about the data.3 “Further, the use of multiple doses in later cohorts have not led to a change in the toxicity profile, which may enable patients to stay on treatment longer and, ultimately, improve outcomes.”
REFERENCES
1. Nabors LB, Lamb LS, Goswami T, Rochlin K, and Youngblood SL. Adoptive cell therapy for high grade gliomas using simultaneous temozolomide and intracranial mgmt-modified γδ t cells following standard postresection chemotherapy and radiotherapy: current strategy and future directions. Front Immunol. Published online February 7, 2024. doi: 10.3389/fimmu.2024.1299044
2. IN8bio Announces Publication on Novel Gamma-Delta T Cell Therapy for Glioblastoma in Frontiers in Immunology. News release. IN8bio. February 14, 2024. https://www.biospace.com/article/releases/in8bio-announces-publication-on-novel-gamma-delta-t-cell-therapy-for-glioblastoma-in-frontiers-in-immunology-/
3. IN8bio Announces Positive INB-200 Phase 1 Data Update in Glioblastoma at the 2023 ASCO Annual Meeting. News release. IN8bio. June 5, 2023. https://investors.in8bio.com/news-releases/news-release-details/in8bio-announces-positive-inb-200-phase-1-data-update
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