Engineered TIL therapy shows early activity in ICI-resistant melanoma

A pooled analysis of two single-arm phase 1 and phase 1/2 trials included 37 patients with advanced melanoma progressing after immune checkpoint inhibitor therapy. Among 15 patients treated at the selected dose, 10 had an objective response, including two complete responses; the pivotal phase 2 cohort is ongoing.

Pooled analysis included 37 treated patients across two trials.
Ten of 15 patients at the selected dose responded.
No dose-limiting toxicities or treatment-related deaths were reported.
A separate pivotal phase 2 cohort is ongoing.

Amsokigene autoleucel (amsoki-cel; OBX-115) is an investigational autologous tumor-infiltrating lymphocyte (TIL) therapy engineered to express membrane-bound interleukin-15 when activated by acetazolamide. The pooled analysis combined a completed single-center phase 1 trial and an ongoing multicenter phase 1/2 trial in patients with advanced melanoma that had progressed after immune checkpoint inhibitor therapy. All 37 treated patients received lymphodepletion, a single amsoki-cel infusion and acetazolamide.

The analysis reported no dose-limiting toxicities, intensive care admissions or treatment-related deaths. Grade 3 or higher treatment-emergent events most commonly included neutropenia (24/37; 64.9%), leukopenia and lymphopenia (21/37 each; 56.8%), and anemia and thrombocytopenia (14/37 each; 37.8%). In the key efficacy set of 15 patients treated at the recommended phase 2 dose, 10 (66.7%; 95% CI, 38–88%) had an objective response, including two complete responses.

These early results suggest antitumor activity with a toxicity profile that warrants further study. The pooled analysis is post hoc, uncontrolled and based on a small efficacy set; a separate pivotal phase 2 cohort remains ongoing. The findings do not establish comparative benefit or support changing current treatment practice.

In practice

For adults with advanced melanoma progressing after immune checkpoint inhibitor therapy, amsoki-cel is an investigational TIL approach with early evidence of activity: 10 of 15 patients treated at the selected dose responded, including two complete responses. The pooled trials reported no dose-limiting toxicities or treatment-related deaths, although grade 3 or higher cytopenias were common. These findings come from small, single-arm cohorts and a post hoc analysis; they do not establish comparative benefit or justify changing treatment practice. A pivotal phase 2 cohort is ongoing.

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Source

Nature Medicine: Regulatable membrane-bound IL-15 engineered TIL cell therapy for immune checkpoint inhibitor-resistant advanced melanoma: pooled analysis of phase 1 and 1/2 trials ↗

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