Obsidian Therapeutics to Present New OBX-115 Data at 2024 ASCO Meeting

Obsidian Therapeutics Inc., a prominent clinical-stage biotechnology firm, has recently disclosed new findings from its ongoing Phase 1 clinical trial concerning OBX-115. This study focuses on a novel engineered tumor-derived autologous T-cell immunotherapy, specifically targeting patients with immune checkpoint inhibitor (ICI)-resistant advanced or metastatic melanoma. The latest data were shared by Dr. Rodabe Amaria, a professor of Melanoma Medical Oncology at The University of Texas MD Anderson Cancer Center, during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.

OBX-115 represents a pioneering approach to T-cell immunotherapy, equipped with pharmacologically regulatable membrane-bound IL15 (mbIL15). The clinical trial, referenced as NCT05470283, is a first-in-human, single-center, dose-escalation study. The updated data, covering a 3-month period relative to the published abstract, offer insights into both the safety and efficacy of OBX-115 for patients grappling with advanced or metastatic melanoma.

Key Safety Findings:
- Across all ten patients infused with OBX-115, no dose-limiting toxicities (DLTs) were reported.
- There were no Grade 4 or higher non-hematologic treatment-emergent adverse events (TEAEs). Only two patients experienced limited Grade 3 non-hematologic TEAEs.
- No cases of cytokine release syndrome, capillary leak syndrome, or immune effector cell-associated neurotoxicity syndrome were observed.
- All patients remained alive at the data cutoff point, with a median follow-up duration of 29.5 weeks, and none required intensive care unit (ICU) support.

Efficacy Insights:
- Among the nine patients evaluated for efficacy, a 44% objective response rate (ORR) was achieved, including two complete responses (CRs) based on investigator-assessed RECIST 1.1 criteria.
- Patients treated with a cell dose greater than 30 × 10^9 cells demonstrated a 50% ORR.
- Disease control, defined as CR, partial response (PR), or stable disease duration of at least 12 weeks post-infusion, was achieved in 100% of the patients.
- Progression-free survival (PFS) was noted to be 75% at 24 weeks.
- Tumor burden reduction was observed in all nine patients, including those with tyrosine kinase inhibitor (TKI)-refractory disease or previously treated brain metastasis.
- Both fresh and cryopreserved OBX-115 products elicited positive responses.

Additional Data:
- The manufacturing process for OBX-115 was robust, even when utilizing tumor tissue obtained via core needle biopsy.
- The median OBX-115 dose manufactured was 100 × 10^9 cells.
- Translational data underscored that the OBX-115 infusion product was optimized for response and persistence. It predominantly contained CD8+ cytotoxic T-cell populations with an effector memory phenotype, a high proportion of CD8+CD39-CD69- (double-negative) "stem-like" progenitor cells, and low levels of exhaustion markers.

These findings indicate that OBX-115 could offer a new therapeutic avenue for patients with heavily pre-treated advanced melanoma, who typically have limited treatment options with low efficacy. OBX-115's positively differentiated safety profile and promising early efficacy data provide hope for these patients.

Obsidian Therapeutics continues to enroll patients with advanced or metastatic melanoma and non-small cell lung cancer (NSCLC) in its ongoing Phase 1/2 multicenter study (NCT06060613). The company aims to build on its initial findings, optimizing the OBX-115 regimen and exploring its potential applications further.