Obsidian’s TIL Therapy Fast Tracked for Metastatic Melanoma
OBX-115 recently demonstrated a 50% ORR at doses over 30 × 109 cells at 29.5 weeks after infusion.
Rodabe Amaria, MD
Credit: MD Anderson Cancer Center
The FDA has granted Fast Track designation to Obsidian Therapeutics’ tumor-infiltrating lymphocyte (TIL) therapy OBX-115 for the potential treatment of metastatic or locally advanced melanoma that is refractory to or has relapsed after PD-1/PD-L1–based immune checkpoint inhibitors.1
“FDA Fast Track Designation underscores the ongoing unmet need for patients with melanoma that has progressed on or after ICI therapy, agnostic of mutational status, and that OBX-115 may have the potential to address that unmet need,” Madan Jagasia, MD, Chief Executive Officer, Obsidian, said in a statement.1 “OBX-115 is poised to be a transformative treatment option due to its patient-centric focus, including compatibility with core needle biopsy tumor tissue procurement and positively differentiated safety and tolerability profile relative to non-engineered TIL cell therapy. We are highly encouraged by the most recent safety and efficacy data presented at the 2024 American Society of Clinical Oncology Meeting. With this designation, we look forward tocontinued collaborative interaction with the FDA as we advance OBX-115 clinical development in the broad post-ICI setting.”
OBX-115 is a novel engineered tumor-derived autologous TIL cell therapy armored with pharmacologically regulatable membrane-bound IL15. It is being evaluated in a first-in-human, single-center study (NCT05470283) at MD Anderson Cancer Center.
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Principal investigator Rodabe Amaria, MD, professor, Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, presented efficacy and safety data from the study at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in June 2024.
These data demonstrated a manageable safety profile of OBX-115, with no dose-limiting toxicities and no grade 4 or higher non-hematologic treatment-emergent adverse events (TEAEs) observed (there were 2 grade 3 cases of TEAEs). There were no confirmed events of cytokine release syndrome, capillary leak syndrome, or immune effector cell-associated neurotoxicity syndrome.
“OBX-115 continues to demonstrate positive safety and efficacy data in additional patients, which is encouraging, given this is a heavily pre-treated patient population with advanced disease. Unfortunately, late-line systemic therapy options offer limited benefit, with ORR of approximately 10% and mPFS of approximately 2–3 months. It is exciting to see a potential new optionemerge for these patients with a positively differentiated safety profile and promising early activity achieved without IL2,” Amaria said in a statement.2
OBX-115 continued to demonstrate efficacy in these additional patients with heavily pretreated, ICI-resistant disease. There were 2 complete responses and a 44% overall response rate (ORR). Patients receiving cell doses of over 30×109 cells had a 50% ORR. At a median follow-up of 29.5 weeks, patients had an overall survival rate of 100%. Progression-free survival at 24 weeks was 75%.
“We believe OBX-115 has the potential to advance the TIL cell therapy field in multiple ways, including enabling non-surgical tumor tissue procurement and abrogating the need for IL2. We are also exploring the ability to re-energize engrafted OBX-115 cells with acetazolamide re-dosing,” Parameswaran Hari, MD, Chief Development Officer, Obsidian, added.2 “We look forward to continuing to build on this momentum and apply key learnings from the first-in-human Phase 1 study to our ongoing Phase 1/2 multicenter study, where we are continuing to explore these attributes and optimize the OBX-115 regimen in melanoma and non-small cell lung cancer.”
