Obsidian Therapeutics has enrolled the first patient in the registration-enabling cohort of its Phase 1/2 Agni-01 trial after reaching agreement with FDA on a potential accelerated approval pathway for its engineered tumour-infiltrating lymphocyte (TIL) therapy for advanced melanoma.

The company said the single-arm study is intended to support a future Biologics License Application (BLA) for amsoki-cel, an investigational cell therapy for patients with immune checkpoint inhibitor-resistant advanced or metastatic melanoma.

The milestone follows encouraging Phase 1/2 results that demonstrated a 67% objective response rate at the recommended Phase 2 dose, including two complete responses in patients with limited treatment options.

FDA alignment marks important development milestone

Obsidian said discussions with FDA resulted in agreement on key aspects of the trial design and manufacturing strategy, allowing the company to begin the registration-enabling cohort using a single-arm study design.

The primary endpoint will be objective response rate, assessed using RECIST v1.1 criteria through blinded independent central review.

Patient enrolment is expected to be completed during the first quarter of 2027, with topline data anticipated before the end of next year.

Parameswaran Hari, chief medical officer at Obsidian Therapeutics, said: “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.”

He added: “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.”

Engineered TIL therapy aims to improve treatment tolerability

Amsoki-cel is an engineered autologous TIL therapy designed to target advanced solid tumours while incorporating membrane-bound IL15 to enhance T cell activity.

Unlike conventional TIL therapies, which typically require high-dose interleukin-2 (IL2) following infusion to support immune cell expansion, Obsidian’s treatment has been developed as an IL2-free regimen. The approach is intended to reduce treatment-related toxicity while supporting outpatient administration.

The therapy also uses lower-dose lymphodepletion and offers the option of obtaining tumour tissue through a less invasive core needle biopsy rather than more extensive surgical procedures.

These features are intended to broaden access to TIL therapy for patients who may not be suitable for existing treatment approaches.

Positive early data support continued development

The registration-enabling study builds on previously reported Phase 1/2 results from the Agni-01 trial.

At the recommended Phase 2 dose, amsoki-cel achieved a 67% objective response rate among evaluable patients, with two complete responses reported in patients with immune checkpoint inhibitor-resistant advanced melanoma.

The company also reported a favourable safety profile, with no dose-limiting toxicities, treatment-related deaths, immune effector cell-associated neurotoxicity syndrome or intensive care unit transfers observed during the study.

In parallel with the melanoma programme, Obsidian is evaluating amsoki-cel in patients with non-small cell lung cancer within the Agni-01 trial. Initial Phase 1 data from that programme are expected during the first half of 2027.

The initiation of the registration-enabling cohort represents an important step towards potential regulatory submission and reflects continued momentum in the development of next-generation engineered TIL therapies for patients with advanced solid tumours.