Obsidian reports a 67% response rate with amsoki-cel in ICI-resistant advanced melanoma, with five ongoing responses at 14.3 months.
Written By: Aasritha Thippavajjala, PharmD
Reviewed By: Pharmacally Editorial Team
Obsidian Therapeutics has reported updated clinical findings for amsokigene autoleucel (amsoki-cel, formerly OBX-115), an investigational engineered tumour-infiltrating lymphocyte (TIL) cell therapy, demonstrating antitumour activity in patients with immune checkpoint inhibitor (ICI)-resistant advanced melanoma. Updated results from the Phase 1/2 Agni-01 study showed an objective response rate (ORR) of 67%, including two complete responses (CRs) and eight partial responses (PRs), among 15 patients treated at the recommended Phase 2 dose (RP2D).
At a median follow-up of 14.3 months, five of the ten responses remained ongoing. Five patients (33%) also maintained deep, ongoing responses at the 12-month landmark. Obsidian presented the findings at the Society for Immunotherapy of Cancer (SITC) 2026 Annual Meeting.
Amsoki-cel: An Engineered TIL Therapy Approach
Amsoki-cel is an investigational autologous TIL cell therapy engineered to express pharmacologically regulatable membrane-bound interleukin-15 (mbIL15). The treatment uses Obsidian’s proprietary cytoDRiVE platform, which enables small-molecule control of therapeutic protein activity.
In amsoki-cel, acetazolamide (ACZ), an oral medication, stabilises a carbonic anhydrase 2 (CA2)-based drug-responsive domain, enabling mbIL15 expression on the T-cell surface. This approach is designed to support T-cell activity and persistence while avoiding systemic interleukin-2 (IL-2) administration.
The treatment also incorporates low-dose lymphodepletion and allows tumour procurement through minimally invasive core needle biopsy (CNB), potentially reducing some procedural and treatment-related burdens associated with conventional TIL therapy.
Agni-01 Demonstrates 67% Objective Response Rate
The multicentre, open-label, single-arm Phase 1/2 Agni-01 study (NCT06060613) evaluated amsoki-cel in adults with advanced melanoma that had progressed following ICI treatment.
The updated efficacy analysis included 15 patients treated at dose level 3 (DL3)/RP2D, comprising six patients from Phase 1 dose optimisation and nine from Phase 2. The data cutoff was September 25, 2026. The population was heavily pretreated, with 93% previously receiving doublet ICI therapy and 73% experiencing disease progression following anti-PD-1 and anti-CTLA-4 combination treatment.
Amsoki-cel achieved an ORR of 67% (10/15), comprising two confirmed CRs and eight confirmed PRs, assessed using RECIST version 1.1. Median progression-free survival (mPFS) was 8.3 months, while median duration of response (mDOR) had not been reached.
Response Durability and Updated Tumour Reduction
The updated analysis highlighted sustained responses in a subset of patients. Since the May 5, 2026, abstract cutoff, one partial response deepened to a 100% reduction in the sum of diameters (SOD) of target lesions at six months following infusion.
Consequently, two patients with partial responses achieved 100% target-lesion reduction, alongside two patients with complete responses. All four responses remained ongoing. At the 12-month landmark, five patients maintained deep, ongoing responses, with tumour reduction ranging from 72% to 100%.
These findings indicate that some patients experienced substantial and sustained tumour regression. However, the small efficacy population limits conclusions about the likelihood of achieving durable benefit across a broader patient population.
Pooled Safety Findings Across 37 Patients
Obsidian reported pooled safety data from 37 patients enrolled in the Phase 1 first-in-human study (NCT05470283) and Phase 1/2 Agni-01, using a separate May 5, 2026, data cutoff.
No dose-limiting toxicities, treatment-related deaths, immune effector cell-associated neurotoxicity syndrome or intensive care unit transfers were reported. One Grade 3 cytokine release syndrome event occurred. Serious treatment-emergent adverse events were reported in ten patients, including Grade 3 or higher serious events in eight.
Haematological toxicities remained an important safety consideration. Grade 3 or higher neutropenia occurred in 64.9% of patients, while leukopenia and lymphopenia each occurred in 56.8%. Grade 3 or higher anaemia and thrombocytopenia were each reported in 37.8%.
Tumour procurement was performed through CNB in ten patients (27%) and surgical resection in 27 (73%). These findings suggest that although the treatment avoids systemic IL-2 administration, substantial haematological toxicity remains associated with the treatment regimen.
Clinical Significance and Development Outlook
Amsoki-cel’s 67% ORR provides an encouraging early clinical signal in ICI-resistant advanced melanoma, particularly given the substantial prior treatment exposure in the efficacy population. Its pharmacologically regulatable mbIL15 mechanism also represents a differentiated approach to engineering TIL therapies.
However, the findings require cautious interpretation. The efficacy analysis involved only 15 patients and lacked a comparator arm. The contribution of mbIL15 regulation to clinical responses has not been independently established, while the pooled safety findings demonstrate considerable haematological toxicity. Comparisons with lifileucel (Amtagvi), the FDA-approved TIL therapy for advanced melanoma, therefore remain premature in the absence of head-to-head evidence.
Obsidian is advancing a registration-enabling cohort within Agni-01, following discussions with the FDA. Enrolment is expected to be completed by the end of the first quarter of 2027, with topline results anticipated by year-end 2027. The company is also investigating amsoki-cel in non-small cell lung cancer, with Phase 1 data expected in the first half of 2027.
The forthcoming registration-enabling results will be important in determining whether the response rate and durability observed in the initial cohort can be reproduced in a larger population and support a future regulatory submission.
References
Obsidian Therapeutics to Present Updated Amsoki-cel Efficacy and Pooled Safety Data in Advanced Melanoma at SITC 2026 Annual Meeting.6 November 2026.
Amaria RN, Chesney JA, Betof AS, 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. 2026.
A Study of OBX-115 in Patients With Advanced Solid Tumors. Clinicaltrailsgov.in NCT06060613.
About the Writer
Aasritha Thippavajjala (Linkedin) is a pharm D student and aspiring medical writer with medical writing, clinical training experience and a strong interest in clinical research and patient safety She has hands-on exposure to clinical pharmacy activities including medication profile assessment, clinical case review, identification of potential drug-related problems, ADR awareness, patient counselling, and clinical documentation. She has also gained experience in medical literature review, evidence synthesis, and scientific communication through her published review article on digital twin-based patient simulation and her poster presentation at the 74th Indian Pharmaceutical Congress. Certified in ICH Good Clinical Practice (E6(R3)) and Scientific Writing in Health Research, she is passionate about applying her clinical knowledge and research skills to medical writing ,clinical research and contributing to accurate, evidence-based healthcare.