On April 9, 2024 Obsidian Therapeutics, Inc., a clinical-stage biotechnology company pioneering engineered cell and gene therapies, reported an update on its Phase 1 first-in-human study of OBX-115 tumor-infiltrating lymphocyte (TIL) cell therapy in patients with advanced or metastatic melanoma, including 25-week median study follow-up safety data and newly detailed efficacy data, during a presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in San Diego, CA (Press release, Obsidian Therapeutics, APR 9, 2024, View Source [SID1234641965]). The poster, "OBX-115 engineered tumor-infiltrating lymphocyte (TIL) cell therapy induced deepening and durable responses without interleukin 2 (IL2) in patients with immune checkpoint inhibitor (ICI)-resistant unresectable or metastatic melanoma," was presented by Rodabe N. Amaria, M.D., professor of Melanoma Medical Oncology at The University of Texas MD Anderson Cancer Center and principal investigator of the study.

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The single-center study (NCT05470283) is evaluating the safety, tolerability, dosing, and efficacy of OBX-115 in patients with ICI-resistant metastatic melanoma. All 6 patients had disease that was primary-resistant to anti–PD-1 therapy, with a median of 2.5 (range, 1–5) lines of prior therapy.

OBX-115 was well-tolerated with a differentiated safety profile from non-engineered TIL cell therapy, which utilizes high-dose IL2:

No dose-limiting toxicities were observed
No Grade 4 or higher non-hematologic events were reported and 2 patients experienced limited Grade 3 events
No confirmed events of cytokine release syndrome, capillary leak syndrome, or ICANS were reported
OBX-115 induced consistently deepening and durable responses:

50% objective response rate and 33% complete response rate using investigator-assessed RECIST 1.1 criteria
All patients experienced tumor burden reduction and meaningful disease control for ≥12 weeks after infusion
All patients were alive and median PFS had not been reached, with 6-month PFS of 67%
Dr. Amaria stated, "The clinical safety and efficacy data from the first 6 patients treated with OBX-115 are promising and demonstrate a meaningful objective response rate. The results are particularly encouraging since OBX-115 is the first engineered TIL cell therapy not requiring IL2 co-administration. OBX-115 has the potential to drive durable responses in patients with ICI-resistant metastatic melanoma, without the well-described toxicity associated with IL2."

"We are highly encouraged by the promising OBX-115 data being shared today, which not only clinically validate Obsidian’s cytoDRiVE technology, but also demonstrate that OBX-115, with its positively differentiated safety profile, has the potential to further expand eligibility for TIL cell therapy and comprehensively address the unmet need in ICI-resistant advanced melanoma," commented Parameswaran Hari, M.D., Chief Development Officer of Obsidian.

In addition to the first-in-human study, Obsidian is actively enrolling patients with metastatic melanoma and NSCLC at multiple sites in its ongoing Phase 1/2 multicenter study. Additional details may be found at clinicaltrials.gov, using identifier: NCT06060613.

Obsidian also has 3 other poster presentations at AACR (Free AACR Whitepaper) 2024:

Title: Trial in progress: A Phase 1/2 study to investigate the safety and efficacy of OBX-115 engineered tumor-infiltrating lymphocyte (TIL) cell therapy in patients (pts) with immune checkpoint inhibitor (ICI)-resistant advanced or metastatic melanoma
Presenting Author: Sajeve S Thomas, Orlando Health Cancer Institute, Orlando, FL

Title: Tumor-infiltrating lymphocytes (TIL) engineered with membrane-bound IL15 (cytoTIL15 cells) exhibit pharmacologically regulatable signal transduction in cis and trans
Presenting Author: Rachel Burga, Obsidian Therapeutics, Inc., Cambridge, MA

Title: Tumor-infiltrating lymphocytes (TIL) engineered with regulatable membrane-bound IL15 (mbIL15) and LIGHT (TNFSF14) show enhanced efficacy in fibroblast-containing cold tumors
Presenting Author: Balazs Koscso, Obsidian Therapeutics, Inc., Cambridge, MA

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. OBX-115 is being investigated in 2 ongoing and enrolling clinical trials in advanced or metastatic melanoma and NSCLC (NCT05470283 and NCT06060613).