Key Findings
Pooled analysis from a completed phase 1 first-in-human (FIH) trial and an ongoing phase 1/2 Agni-01 trial showed that 10 out of 15 patients in the Key Efficacy Set (treated at the recommended phase 2 dose, or RP2D) achieved objective responses, representing an ORR of 66.7% (95% CI 38–88%), including two complete responses. In the Agni-01 phase 2 preliminary group, the ORR was 66.7% (6/9). No dose-limiting toxicities, treatment-related mortality, or requirements for ICU care were reported across the 37 treated patients.
Technical Details
Amsoki-cel (OBX-115) is an autologous tumor-infiltrating lymphocyte (TIL) therapy engineered to express membrane-bound interleukin-15 (mbIL15). The expression is controlled by a carbonic anhydrase-2 (CA2) drug-responsive domain (DRD). In the basal state, the mbIL15-DRD fusion protein is degraded; however, the administration of acetazolamide (ACZ), a CA2 inhibitor, stabilizes the DRD and induces mbIL15 expression on the cell surface. This mechanism allows for pharmacologic regulation of cell expansion and persistence without the need for systemic interleukin-2 (IL-2).
Background and Context
Standard non-engineered TIL therapies require high-dose intravenous IL-2 for expansion and efficacy, which often causes substantial clinical toxicity and limits patient eligibility. Amsoki-cel addresses this by using regulatable mbIL15, which results in a more robust manufacturing process and a T cell phenotype that is more stem-like and less terminally exhausted than conventional TILs. The study population consisted of patients with advanced melanoma who were resistant to immune checkpoint inhibitors (ICI).
Significance and Outlook
The most common grade 3 or higher treatment-emergent adverse events were neutropenia (64.9%), leukopenia/lymphopenia (56.8% each), and anemia/thrombocytopenia (37.8% each). While an early patient experienced vasogenic edema in a previously irradiated brain metastasis—leading to an 80% reduction in maximum amsoki-cel dose and a 75% reduction in ACZ dose—subsequent dose re-escalation demonstrated favorable safety. A separate phase 2 pivotal Agni-01 cohort is currently ongoing.
Source: https://doi.org/10.1038/s41591-026-04743-6
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