First Patient Enrolled in Registration-Enabling Amsoki-Cel Melanoma Cohort

The first patient has been enrolled in the registration-enabling cohort of the phase 1/2 Agni-01 study (NCT06060613) evaluating amsokigene autoleucel (amsoki-cel; formerly OBX-115) in patients with immune checkpoint inhibitor (ICI)-resistant advanced or metastatic melanoma, according to a news release from Obsidian Therapeutics, Inc.¹

The registration-enabling cohort is part of the ongoing multicenter phase 1/2 trial evaluating amsoki-cel, an engineered autologous tumor-infiltrating lymphocyte (TIL) cell therapy, at the recommended phase 2 dose (RP2D) in patients with ICI-resistant advanced melanoma. The company adopted a single-arm trial design intended to support a future biologics license application (BLA) submission via the accelerated approval pathway following discussions with the FDA.

“We have obtained alignment with the FDA across key trial design and manufacturing considerations, including drug potency assay, to proceed with the registration-enabling cohort in support of the single-arm accelerated approval pathway for amsoki-cel in advanced melanoma,” Parameswaran Hari, MD, MS, chief medical officer of Obsidian, said in the news release.

Prior Efficacy and Safety Findings

Initiation of the registration-enabling cohort follows earlier phase 1/2 results from the Agni-01 study, in which amsoki-cel demonstrated a 67% ORR at the RP2D of 1-100 × 10⁹ cells (10 of 15 patients), including 2 complete responses, in a population with advanced melanoma.² At a median study follow-up of 18.6 weeks, median duration of response (DOR) was not reached (range, 4.6+ to 55.1+ weeks)

The therapy also showed a consistent, favorable safety profile using low-dose lymphodepletion and no interleukin-2 (IL-2) in the treatment regimen; no dose-limiting toxicities, treatment-related deaths, immune effector cell-associated neurotoxicity syndrome, or intensive care unit transfers were observed in the trial. Four serious adverse events were reported in 3 of these patients; there was 1 case of grade 3 cytokine release syndrome and 1 case of grade 3 immune-related hypoxia which responded to short-course steroids.

Study Design

Patients in the refractory melanoma cohort must have unresectable or metastatic melanoma with documented radiographic progression after systemic therapy containing a PD-1/PD-L1 blocking antibody but cannot have more than 2 prior lines of systemic therapy, although neoadjuvant/adjuvant treatment is not counted unless the patient had disease progression during or within 12 weeks after the last dose of the adjuvant ICI.³ Patients with BRAF mutations are not required to have received prior BRAF inhibitors, and they cannot have disease progression on a BRAF/MEK inhibitor regimen that was given as the most recent line of therapy. Patients with uveal melanoma are not eligible.

Patients will receive lymphodepletion including cyclophosphamide and fludarabine before amsoki-cel infusion, followed by short courses of acetazolamide.

The primary end point is objective response rate (ORR) per RECIST v1.1, assessed by blinded independent central radiologist review. Secondary end points include DOR, progression-free survival, and overall survival. Enrollment in the cohort is anticipated to be completed by the end of the first quarter of 2027, with topline data expected by the end of 2027.¹

Mechanism and Broader Development Context

The therapy's membrane-bound IL-15 armoring is intended to enhance TIL persistence, antitumor activity, and clinical safety vs earlier-generation TIL therapies, according to the company. Unlike the approved TIL therapy lifileucel (Amtagvi), the amsoki-cel regimen does not include IL-2, is compatible with less invasive core needle biopsy for tumor tissue procurement, and uses exclusively low-dose lymphodepletion compatible with outpatient administration, which could support use across a broad patient population. Two patients in the previous melanoma cohort had tissue procured by core needle biopsy, and 4 had lymphodepletion in the outpatient setting.²

Beyond melanoma, Obsidian is also evaluating amsoki-cel in patients with non–small cell lung cancer (NSCLC) within the Agni-01 trial, with phase 1 data in that population expected in the first half of 2027.¹

REFERENCES

1. Obsidian Therapeutics Announces First Patient Enrolled in the Registration-Enabling Cohort of Phase 1/2 Agni-01 Study Evaluating Amsoki-cel (OBX-115) in Advanced Melanoma. News release. Obsidian Therapeutics, Inc. Business Wire. August 5, 2026. Accessed August 5, 2026.

2. Betof AS, Chesney JA, In GK, et al. OBX-115 engineered tumor-infiltrating lymphocyte (TIL) cell therapy with regulatable membrane-bound IL15 (mbIL15) in patients with advanced melanoma that has progressed on/after immune checkpoint inhibitors. J Clin Oncol. 2026;supp 16:9507. doi:10.1200/JCO.2026.44.16_suppl.9507

3. Safety and Efficacy of OBX-115 in Advanced Solid Tumors (Agni-01). ClinicalTrials.gov. Updated July 16, 2026. Accessed August 6, 2026. https://clinicaltrials.gov/study/NCT06060613