Engineered TIL Therapy Shows Early Activity in Checkpoint Inhibitor–Resistant Melanoma

Investigational amsokigene autoleucel (amsoki-cel, formerly OBX-115; Obsidian Therapeutics, Inc) produced confirmed responses in 10 of 15 patients (66.7%) with advanced melanoma that had progressed after immune checkpoint inhibitor (ICI) therapy. The updated phase 1/2 Agni-01 trial (NCT06060613) results, presented at the 2026 Society for Immunotherapy of Cancer (SITC) Annual Meeting, offer an early look at an engineered tumor-infiltrating lymphocyte (TIL) regimen that uses lower-dose lymphodepletion and omits systemic IL-2.¹

Five Patients Remained in Response at 12 Months

The efficacy analysis included 6 patients from the phase 1 and 9 from phase 2 segments who received the recommended phase 2 regimen in the open-label, single-arm Agni-01 study. Fourteen of the 15 patients had previously received dual checkpoint blockade, and 11 had experienced progression after a programmed cell death PD-1 inhibitor combined with a cytotoxic T-lymphocyte–associated protein 4 inhibitor.^1,2

Investigators recorded 2 confirmed complete responses and 8 confirmed partial responses. At 12 months after infusion, 5 of the 15 patients (33.3%) remained in response. At a median follow-up of about 8.3 months, median progression-free survival was 8.1 months and median duration of response had yet to be reached. The small cohort and single-arm design limit conclusions about how long responses will last in a broader population and how the regimen compares with other options after checkpoint inhibitor progression.^1,2

Cytopenias Remained Common in the Pooled Safety Analysis

The safety analysis included 37 patients treated across 2 studies: 17 from the single-center first-in-human phase 1 trial (NCT05470283) and 20 from Agni-01. The pooled group included patients who received different cell doses and lymphodepletion regimens. In the peer-reviewed analysis published in Nature Medicine, 33 patients (89.2%) had a grade 3 or higher treatment-emergent adverse event (TEAE), and 10 (27.0%) had a serious TEAE. Grade 3 or higher neutropenia occurred in 24 patients (64.9%), and thrombocytopenia of that severity occurred in 14 (37.8%).²

The investigators reported 1 case of grade 3 cytokine release syndrome. They observed no dose-limiting toxicities, cases of immune effector cell–associated neurotoxicity syndrome, intensive care unit admissions, or treatment-related deaths. Among the 26 patients who received lower-dose lymphodepletion, 17 (65.4%) experienced grade 3 or higher hematologic TEAEs. The frequency of severe cytopenias and the observed cytokine release syndrome keep blood count surveillance and postinfusion monitoring central to the regimen.^1,2

How Acetazolamide Fits Into the Regimen

Amsoki-cel is made from a patient’s own tumor-infiltrating lymphocytes, engineered to express membrane-bound IL-15. Acetazolamide stabilizes the engineered protein, allowing IL-15 to appear on the cell surface and support T-cell expansion and persistence. The trial protocol paired a single amsoki-cel infusion with acetazolamide dosing after cyclophosphamide and fludarabine lymphodepletion. In the pooled safety population, investigators used tissue from core needle biopsies to manufacture the product for 10 patients and tissue from surgical excision for the other 27. Four patients received lower-dose lymphodepletion as outpatients.²

The regimen differs from that of FDA-approved lifileucel (Amtagvi; Iovance Biotherapeutics), which calls for inpatient administration, lymphodepletion prior to infusion, and high-dose aldesleukin following infusion. Omitting aldesleukin would remove a postinfusion medication from the treatment schedule. For oncology pharmacy teams, the practical question is how much care can move outside the hospital given the ongoing need to monitor for cytopenias and infusion-related complications. The 4 outpatient cases describe where lymphodepletion was delivered. They provide limited evidence about delivering the entire treatment course in an outpatient setting.^2,3

Agni-01 Continues With a Registration-Enabling Cohort

A separate trial-in-progress poster, SITC abstract 570, described the registration-enabling phase 2 cohort of Agni-01 in patients with ICI-resistant advanced melanoma. The single-arm cohort aims to enroll approximately 86 patients. Its primary end point is objective response rate assessed by blinded independent central review. Secondary end points include duration of response and manufacturing feasibility, a measure that will help show how consistently the team can produce a patient-specific therapy across study sites.⁴

REFERENCES

1. Amaria RN, Betof AS, In GK, et al. OBX-115 (amsokigene autoleucel; amsoki-cel) TIL cell therapy in ICI-resistant advanced melanoma: pooled safety and updated efficacy with minimally invasive tumor tissue procurement, low-dose lymphodepletion, and IL2-free regimen. News release. Obsidian Therapeutics. October 2, 2026. Accessed November 9, 2026. https://ir.obsidiantx.com/news-releases/news-release-details/obsidian-therapeutics-present-updated-amsoki-cel-obx-115-phase

2. Amaria, Rodabe & Chesney, Jason & Betof, Allison & In, et. al, 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. Nature Medicine. 1-12. 10.1038/s41591-026-04743-6

3. Amtagvi. Prescribing information. Iovance Biotherapeutics, Inc; 2024. https://www.fda.gov/media/176417/download?attachment

4. In GK, et al. Trial in progress: Agni-01 phase 2 cohort of OBX-115 (amsokigene autoleucel; amsoki-cel) tumor-infiltrating lymphocyte (TIL) cell therapy in patients with ICI-resistant advanced melanoma. Poster presented at: Society for Immunotherapy of Cancer 41st Annual Meeting; November 7, 2026; Phoenix, AZ. Abstract 570. https://obsidiantx.com/publications_posts/trial-in-progress-agni-01-phase-2-cohort-of-obx-115-amsokigene-autoleucel-amsoki-cel-tumor-infiltrating-lymphocyte-til-cell-therapy-in-patients-with-ici-resistant-advanced-melanoma/