Obsidian Therapeutics Enrolls First Patient in Registration-Enabling Cohort for Amsoki-cel TIL Therapy in Advanced Melanoma
核心洞察
Obsidian Therapeutics (搜索) has enrolled the first patient in the registration-enabling cohort of the Phase 1/2 Agni-01 study evaluating amsoki-cel in ICI-resistant advanced melanoma (搜索).
The single-arm trial design, aligned with the FDA, is intended to support a future BLA submission via the accelerated approval pathway.
Prior Phase 1/2 data showed a 67% objective response rate at the recommended Phase 2 dose, including two complete responses, with a favorable safety profile.
Obsidian Therapeutics (搜索), Inc. announced the first patient has been enrolled in the registration-enabling cohort of the Phase 1/2 Agni-01 multicenter study evaluating amsokigene autoleucel (搜索) (amsoki-cel, formerly OBX-115) in patients with immune checkpoint inhibitor (ICI)-resistant advanced or metastatic melanoma. The Cambridge, Massachusetts-based biopharmaceutical company has aligned with the U.S. Food and Drug Administration on key trial design and manufacturing considerations, including drug potency assay, to pursue a single-arm trial design intended to support a future Biologics License Application (BLA) submission under the accelerated approval pathway.
"We have obtained alignment with the US Food and Drug Administration 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 (搜索)," said Parameswaran Hari, M.D., M.S., Chief Medical Officer of Obsidian. "Enrolling the first patient in this cohort is an important step toward bringing a patient-centric tumour-infiltrating lymphocyte treatment regimen to patients with difficult-to-treat ICI-resistant advanced melanoma."
Engineered TIL Therapy with Differentiated Features
Amsoki-cel is a novel engineered tumor-derived autologous T cell immunotherapy armored with pharmacologically regulatable membrane-bound IL15 (搜索) (mbIL15), developed using Obsidian's proprietary cytoDRiVE technology platform. The cytoDRiVE platform is designed to precisely regulate the timing and level of protein function using FDA-approved small-molecule drugs.
The therapy is distinguished by several patient-centric features, including an IL2-free regimen, the option for less-invasive core needle biopsy tumor tissue procurement, and exclusively low-dose lymphodepletion compatible with outpatient administration. Hari noted, "We believe amsoki-cel has the potential to serve a broad patient population given its IL2-free regimen, option for less-invasive core needle biopsy tumour tissue procurement, and exclusively low-dose lymphodepletion compatible with outpatient administration."
Compelling Phase 1/2 Efficacy and Safety Data
The initiation of the registration-enabling cohort follows positive Phase 1/2 results from the Agni-01 study. Amsoki-cel demonstrated strong efficacy with a 67% objective response rate (ORR) at the recommended Phase 2 dose (RP2D), with 10 of 15 patients responding, including two complete responses. These results were achieved in a patient population characterized by high unmet need and difficult-to-treat advanced melanoma (搜索).
The safety profile has been consistently favorable, with low-dose lymphodepletion and no IL2 in the treatment regimen. Notably, there were no reported dose-limiting toxicities, treatment-related mortality, immune effector cell-associated neurotoxicity syndrome (ICANS), or ICU transfers.
Registration-Enabling Cohort Design and Timeline
The single-arm registration-enabling cohort is part of the ongoing Agni-01 multicenter Phase 1/2 study (NCT06060613) and is designed to further evaluate the safety and efficacy of amsoki-cel at the RP2D in patients with ICI-resistant advanced melanoma (搜索). The primary endpoint is objective response rate as measured per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) by blinded independent central radiologist review (BICR).
Enrollment in the registration-enabling cohort is anticipated to be completed by the end of Q1 2027, with topline data expected by year-end 2027.
Expansion into Non-Small Cell Lung Cancer (搜索)
Beyond melanoma, Obsidian is also investigating amsoki-cel in patients with non-small cell lung cancer (搜索) (NSCLC) within the Agni-01 trial. Phase 1 data for the NSCLC cohort are expected in the first half of 2027, potentially broadening the therapeutic reach of this engineered TIL approach to additional solid tumor indications.