Obsidian Therapeutics has enrolled the first patient in a registration-enabling cohort of its Phase 1/2 Agni-01 trial, moving its experimental TIL cell therapy amsoki-cel into the next stage of development for patients with advanced melanoma who no longer respond to immune checkpoint inhibitors.

 

The company said the decision follows discussions with the U.S. Food and Drug Administration and calls for a single-arm trial designed to support a potential future biologics license application (BLA) and an accelerated approval pathway.

 

The move comes after encouraging results from the ongoing Agni-01 study. At the recommended Phase 2 dose, amsoki-cel produced a 67% objective response rate, with 10 of 15 patients responding, including two complete responses.

 

“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. 

 

"Enrolling the first patient in this cohort is an important step toward bringing a patient-centric TIL treatment regimen to patients with difficult-to-treat ICI-resistant advanced melanoma,” said Parameswaran Hari, Chief Medical Officer of Obsidian. 

 

“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 tumor tissue procurement, and exclusively low-dose lymphodepletion compatible with outpatient administration. We anticipate reporting topline data from the registration-enabling cohort by year-end 2027.”

 

The new cohort is part of the multicenter Agni-01 Phase 1/2 trial, which is evaluating amsoki-cel in patients with immune checkpoint inhibitor-resistant advanced or metastatic melanoma.

 

The registration-enabling cohort will further assess the therapy at its recommended Phase 2 dose. Its primary endpoint is objective response rate, measured under RECIST v1.1 by blinded independent central radiologist review.

 

Obsidian expects to complete enrollment by the end of the first quarter of 2027, with topline results anticipated by the end of 2027.

 

The registration push follows positive Phase 1/2 data in a patient population with few treatment options.

 

At the recommended Phase 2 dose, amsoki-cel achieved a 67% objective response rate among 15 patients. Two patients achieved complete responses.

 

The company also reported a favorable safety profile, including no dose-limiting toxicities, treatment-related deaths, immune effector cell-associated neurotoxicity syndrome or intensive-care-unit transfers.

 

Amsoki-cel is designed to overcome some of the limitations of conventional TIL therapy. The investigational treatment uses engineered tumor-infiltrating lymphocytes armored with pharmacologically regulatable membrane-bound interleukin-15, or mbIL15.

 

Obsidian says the approach could offer several potential advantages, including an IL-2-free treatment regimen, low-dose lymphodepletion and the option of obtaining tumor tissue through a less-invasive core needle biopsy.