Summary
A pooled analysis of two early-stage trials reported objective responses in 10 of 15 patients with advanced melanoma treated with the investigational TIL therapy amsoki-cel at its recommended dose. The small, non-randomized analysis also found frequent severe blood-related side effects, while a larger trial cohort is ongoing.
A pooled analysis of two early-stage trials reports that 10 of 15 patients with advanced melanoma that had progressed after immune checkpoint inhibitor (ICI) treatment responded to amsoki-cel, an investigational engineered tumor-infiltrating lymphocyte (TIL) therapy. The analysis, published in Nature Medicine, included patients treated at the therapy’s recommended phase 2 dose; two responses were complete. The studies were small and had no comparison group, so the results are an early clinical signal rather than a measure of benefit relative to other treatments.
How amsoki-cel regulates IL-15
TIL therapy uses immune cells taken from a patient’s tumour, expanded in a laboratory and returned by infusion. Amsoki-cel modifies these cells to carry membrane-bound interleukin-15 (mbIL-15), a signal that can support the expansion and persistence of immune cells. The researchers engineered the IL-15 protein to be regulated by a drug-responsive domain: acetazolamide (ACZ) stabilizes the domain, enabling mbIL-15 expression on the cell surface.
This approach is designed to replace high-dose systemic interleukin-2, which has been used to support conventional TIL therapy and can cause substantial toxicity. ACZ can also be given again after the infusion to prompt further mbIL-15 expression. The treatment combines the engineered cells with lymphodepleting chemotherapy, which reduces existing immune cells before infusion.
The report combines a completed, single-centre phase 1 study and the ongoing multicentre phase 1/2 Agni-01 trial. Both were open-label, single-arm studies, and the pooled analysis was conducted after the trials’ planned analyses. Across them, 37 patients received amsoki-cel. The efficacy group highlighted by the paper comprised 15 Agni-01 patients treated at the recommended dose: six from phase 1 and nine from phase 2.
Responses and safety in the recommended-dose group
Investigators assessed tumour response using RECIST version 1.1. Ten of the 15 patients had an objective response, an overall response rate of 66.7% (95% confidence interval 38–88%); this included two complete and eight partial responses. Four other patients had stable disease. Median follow-up for this group was 8.3 months, and the reported median progression-free survival was 8.1 months (95% confidence interval 3.9 months to not estimable).
Across all 37 treated patients, the researchers reported no dose-limiting toxicities, intensive-care treatment or treatment-related deaths. Severe treatment-emergent adverse events were nevertheless common: 33 patients (89.2%) had at least one grade 3 or higher event, with blood-related events among the most frequent. Ten patients had serious adverse events, including eight with grade 3 or higher events. The treatment also includes lymphodepleting chemotherapy, which the authors note is consistent with the blood-related side effects observed.
Dosing changed during the early trials. After the first treated patient developed vasogenic swelling around a previously irradiated brain metastasis alongside rapid lymphocyte expansion, the protocol reduced the maximum cell dose by 80% and the ACZ dose by 75%; doses were later increased in subsequent study stages.
What the results mean
The response rate is encouraging enough to support further study, but it comes from only 15 patients treated at the recommended dose, in trials without random assignment or a control group. The ongoing pivotal Agni-01 cohort is intended to provide a larger assessment. The researchers also describe the proposed contribution of regulated mbIL-15 to tumour activity as a mechanism supported by laboratory and clinical observations, but not directly established by these trials. Further follow-up and study will be needed to clarify how durable the responses are and how the treatment performs in a larger group.