Amtagvi (lifileucel)

P3, N=360, Recruiting, Immatics US, Inc. | N=96 --> 360

P2, N=100, Active, not recruiting, Iovance Biotherapeutics, Inc. | Recruiting --> Active, not recruiting

P3, N=96, Recruiting, Immatics US, Inc.

All individuals received cyclophosphamide/fludarabine lymphodepletion, lifileucel, and 6 or fewer IL-2 infusions. In this cohort study, lifileucel treatment was frequently complicated by purpuric morbilliform eruptions, which were prognostically favorable and associated with short-term response. The lifileucel-associated eruption may be a peritreatment efficacy marker, assessable during the TIL treatment hospitalization prior to traditional 42-day restaging.

The recent U.S. FDA approval of lifileucel, a non-engineered, autologous tumor-infiltrating lymphocyte (TIL) therapy, for unresectable or metastatic melanoma represents a major milestone for cellular therapies in solid tumors...OBX-115, designed with regulatable membrane-bound IL-15 expression, eliminates the need for IL-2 infusion and has shown early clinical activity. KSQ-001EX uses CRISPR/Cas9 to inactivate SOCS1, while KSQ-004EX additionally targets Regnase-1 to enhance TIL function...TIL therapy remains among the most promising strategies in melanoma and solid tumors after immunotherapy failure. Ongoing research aims to optimize cell dose, phenotype, tumor procurement, treatment sequencing, and rational combinations to improve durable benefit.

P1, N=40, Active, not recruiting, Iovance Biotherapeutics, Inc. | Recruiting --> Active, not recruiting

TIL-based adoptive cell therapy is now a promising, personalized treatment for advanced melanoma after anti-PD-1 therapy has failed. Future studies should focus on identifying reliable biomarkers, improving TIL products, combining therapies to change the tumor environment, and making manufacturing more efficient to ensure more patients can safely access TIL therapy.

P1, N=2, Active, not recruiting, Richard Wu | Trial completion date: Dec 2025 --> Dec 2026

The 2024 FDA approval of Lifileucel (Amtagvi), a commercially manufactured autologous TIL product, marks a key milestone in integrating advanced therapy medicinal products (ATMPs) into routine care for solid tumours...A nationally coordinated effort is required to harmonise clinical prioritisation strategies, maintain oversight by multidisciplinary specialist tumour boards, and consider investment in future-proof decentralised manufacturing capacity. Collaborations and peer support such as through the Advanced Therapy Treatment Centre (ATTC) Network will facilitate phased, experience-led rollout with equity-focused service design.

P1/2, N=69, Not yet recruiting, Iovance Biotherapeutics Inc.

P1, N=30, Recruiting, Memorial Sloan Kettering Cancer Center | N=20 --> 30

This constituted only the second approval of a cell therapy in a solid tumor following lifileucel in melanoma and demonstrated the potential of cell therapies in sarcomas...However, the broader application of these therapies is hindered by the lack of targetable sarcoma-restricted immunogenic epitopes, spatiotemporal intratumoral heterogeneity, and a profoundly immunosuppressive tumor microenvironment that impedes effector-cell trafficking, expansion and persistence. While cell therapies hold promise for integration into precision medicine approaches for sarcomas, their successful implementation will require careful evaluation of clinical feasibility, logistical considerations and cost-effectiveness to optimize patient outcomes.