The Promise of OBX-115, a Novel TIL Therapy, in Melanoma

Rodabe Amaria, MD, medical oncologist in the Department of Melanoma Medical Oncology, Division of Cancer Medicines, at MD Anderson Cancer Center, discusses the current role of OBX-115, a novel engineered tumor infiltrating lymphocyte (TIL) therapy, and how it compares with other agents being developed and designed for the treatment of patients with checkpoint inhibitor-resistant metastatic melanoma.

Traditional TIL therapies typically require toxic high-dose interleukin-2 (IL2). However, OBX-115 uses a regulated IL15 system and eliminates the need for this harmful cytokine. According to Amaria, this offers an improved safety profile.

OBX-115 is currently being investigated in a phase 1 study (NCT05470283). Findings were previously presented at the 2024 American Society of Clinical Oncology Annual Meeting, showing that in patients with unresectable or metastatic melanoma resistant to immune checkpoint inhibitors (n = 9), the combination of OBX-115 plus acetazolamide led to an objective response rate (ORR) of 44.4%, including complete response and partial response rates of 22.2% each. For patients given 30 billion cells at OBX-115 infusion (n = 6), the ORR was 50%.

A total of 55.6% of patients had stable disease that lasted for at least 12 weeks, and no patients had progressive disease, translating to a disease control rate of 100%. Additionally, the progression-free survival (PFS) rate at 24 weeks was 75%.

For safety, findings showed that at a median follow-up of 29.5 weeks (range, 13.0-69.3), no treatment- or disease-related mortality were reported. No patients required admission to an intensive care unit, no dose-limiting toxicities were reported, and no cases of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or capillary leak syndrome were seen.

In the interview, Amaria notes that when compared with other TIL therapies, OBX-115 is engineered and does not require the use of interleukin-2, which offers an improved safety profile.

REFERENCE

Amaria RN, McQuade JL, Davies MA, et al. OBX-115, an interleukin 2 (IL2)-sparing engineered tumor-infiltrating lymphocyte (TIL) cell therapy, in patients (pts) with immune checkpoint inhibitor (ICI)-resistant unresectable or metastatic melanoma. J Clin Oncol. 2024;42(suppl 16):9515. doi:10.1200/JCO.2024.42.16_suppl.9515