On June 2, 2025 Obsidian Therapeutics, Inc., a clinical-stage biotechnology company pioneering engineered cell and gene therapies, reported initial Phase 1 safety and efficacy data from the Phase 1/2 Agni-01 multicenter study of OBX-115, a novel engineered tumor-derived autologous T cell immunotherapy (tumor-infiltrating lymphocyte [TIL] cell therapy) armored with pharmacologically regulatable membrane-bound IL15 (mbIL15), in patients with immune checkpoint inhibitor (ICI)-resistant advanced or metastatic melanoma (NCT06060613) (Press release, Obsidian Therapeutics, JUN 2, 2025, View Source [SID1234653654]). These data, summarized below, will be presented in a rapid oral presentation (abstract 9517) delivered by Jason A. Chesney, M.D., Ph.D., Director and Chief Administrative Officer of UofL Health – Brown Cancer Center/Oncology Service Line at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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Obsidian is also presenting a poster for abstract 9519 summarizing translational data from the Phase 1 first-in-human single-center study of OBX-115 (NCT05470283, enrollment completed) in ICI-resistant advanced melanoma.

Summary of OBX-115 Safety and Efficacy Data (March 26, 2025 data cutoff):

Advancing a More Patient-centric TIL Cell Therapy Regimen in Heavily Pre-treated Advanced Melanoma Patient Population

Patients had disease that was predominantly ICI primary-resistant, with a median of 4 (range, 1–6) lines of prior systemic therapy, including a median of 2 (1–5) lines of prior ICI therapy (n=11).
10 patients received low-dose lymphodepletion (approximately 50% less Cyclophosphamide relative to non-engineered TIL), including 1 in the outpatient setting.
Acetazolamide (ACZ) redosing following initial OBX-115 infusion to drive re-activation of OBX-115 cells was tolerable and safe enough to administer at home.
OBX-115 Continues to Deliver Positively Differentiated Safety Profile Relative to Non-engineered TIL; No IL2, No Treatment-related Mortality:

No dose-limiting toxicities were observed at any dose level.
No Grade 4 or higher nonhematologic treatment-related adverse events (TRAEs) were reported; 5 patients experienced limited Grade 3 nonhematologic TRAEs.
No confirmed events of cytokine release syndrome or infusion-related reaction higher than Grade 2; no capillary leak syndrome or immune effector cell-associated neurotoxicity syndrome were reported.
No treatment-related ICU transfer, no treatment-related mortality.
OBX-115 Maintains Consistent Efficacy Profile Without IL2 and With Low-dose Lymphodepletion in Anti-PD-1-resistant Advanced Melanoma; Dose Level 3 (RP2D) To Be Further Explored in Phase 2

Encouraging efficacy profile observed at the RP2D (n=6)
66.7% ORR, including 1 confirmed CR and 3 confirmed PRs (investigator-assessed RECIST 1.1 criteria)
Durable clinical benefit, including 3 of 4 responses ongoing at week 24 / data cutoff (median duration of response not reached)
100% disease control rate, defined as stable disease or better for ≥12 weeks post-infusion
36.4% objective response rate (ORR) across all dose levels (n=11)
Majority had reduction in tumor burden reduction: 83% at RP2D; 73% across all dose levels.
Dr. Chesney commented, "It is very encouraging to see the promising safety and efficacy profile for OBX-115, now observed in the Agni-01 multicenter study. As a highly differentiated, IL2-sparing TIL cell therapy that is compatible with low-dose lymphodepletion, OBX-115 has the potential to transform the treatment landscape and broaden the eligible population for patients with high unmet need."

"The exciting results from OBX-115 in ICI-resistant advanced melanoma further indicate that OBX-115 has promising therapeutic potential, and that ACZ redosing is well-tolerated and has the potential to re-activate and re-expand persistent OBX-115 TIL," commented Parameswaran Hari, M.D., Chief Development Officer of Obsidian. "We look forward to exploring the go-forward melanoma RP2D in Phase 2, and continuing to evaluate OBX-115 in a Phase 1 cohort of patients with advanced non-small cell lung cancer, where we believe the potential impact from an IL2-sparing TIL cell therapy is clinically significant and may expand patient eligibility."

Obsidian is actively enrolling patients with advanced or metastatic melanoma and non-small cell lung cancer (NSCLC) at multiple sites in its ongoing Phase 1/2 Agni-01 multicenter study. Additional details may be found at clinicaltrials.gov, using identifier: NCT06060613.

About OBX-115

Obsidian’s lead investigational cytoTIL15 program, OBX-115, is a novel engineered tumor-derived autologous T cell immunotherapy (tumor-infiltrating lymphocyte [TIL] cell therapy) armored with pharmacologically regulatable membrane-bound IL15 (mbIL15). OBX-115 has the potential to become a meaningful therapeutic option for patients with advanced or metastatic melanoma and other solid tumors by leveraging the expected benefits of mbIL15 and Obsidian’s proprietary, differentiated manufacturing process to enhance persistence, antitumor activity, and clinical safety of TIL cell therapy. Obsidian is investigating OBX-115 in the phase 1/2 Agni-01 multicenter trial in patients with advanced solid tumors (NCT06060613).