ASCO 2026 | OBX-115 TIL therapy in checkpoint inhibitor-refractory advanced melanoma
Allison Betof Warner, MD, Stanford University, Stanford, CA, discusses Phase II results from Agni-01 (NCT06060613), evaluating OBX-115, an engineered tumor-infiltrating lymphocyte (TIL) therapy expressing regulatable membrane-bound IL-15, in patients with advanced non-uveal melanoma progressing on or after immune checkpoint inhibitor therapy. Results demonstrated encouraging efficacy with a high objective response rate, durable responses, and a manageable safety profile with no dose-limiting toxicities or treatment-related mortality. This interview took place during the 2026 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.
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Transcript
Conventional TIL therapy, we know that we take patients’ own tumor-infiltrating lymphocytes, expand them ex vivo in the lab, and then give them back to a patient. But that requires the use of high-dose IL-2 to stimulate those cells to proliferate and to do their work. We’ve been looking for a long time for a way to either minimize the exposure to high-dose IL-2 or actually eliminate it completely because that’s actually the most toxic part of this regimen and actually really limits the number of patients that we can treat with TIL therapy...
Conventional TIL therapy, we know that we take patients’ own tumor-infiltrating lymphocytes, expand them ex vivo in the lab, and then give them back to a patient. But that requires the use of high-dose IL-2 to stimulate those cells to proliferate and to do their work. We’ve been looking for a long time for a way to either minimize the exposure to high-dose IL-2 or actually eliminate it completely because that’s actually the most toxic part of this regimen and actually really limits the number of patients that we can treat with TIL therapy. So OBX115 takes those same TIL cells out of a patient’s tumor, inserts a transgene that expresses membrane-bound IL-15 conjugated to a drug regulation domain. At baseline, those cells express that molecule, and it degrades at baseline because that’s unstable. When we give the patient oral acetazolamide, which is just an FDA-approved diuretic medication, it stabilizes the drug regulation domain, and that then allows the membrane-bound IL-15 to translocate to the membrane. It signals in both cis and trans to activate the same cell as well as nearby NK and CD8 cells and turn them on without giving the patient systemic IL-2.
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