Amtagvi (lifileucel)

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.

P2, N=100, Recruiting, Iovance Biotherapeutics, Inc.

For solid cancers, these comprise the antibody-drug-conjugate Mirvetuximab Soravtansine for platinum-resistant ovarian cancer, the monoclonal antibody Zolbetuximab for Claudin-18.2 positive gastric adenocarcinoma and the checkpoint inhibitor Tislelizumab for esophageal squamous cell carcinoma. For the treatment of relapsed or refractory hematologic B cell malignancies, the use of bispecific T cell engaging antibodies like the BCMA-CD3 targeting Teclistamab and CD20-CD3 targeting Glofitamab were approved by the EMA recently.Combinatorial approaches of conventional chemotherapy and checkpoint inhibitors for the treatment of cholangiocarcinoma, urothelial carcinoma and endometrial carcinoma received recent approval.A CD38 antibody-based bridging therapy for the treatment of newly diagnosed multiple myeloma and the Glofitamab-based approach in combination with Gemcitabine and Oxaliplatin for relapsed DLBCL are the latest additions for hematologic malignancies after promising clinical trials.The first T cell products for the treatment of solid cancers using either tumor-infiltrating lymphocytes or TCR-engineered peripheral blood T cells were approved by the FDA in 2024, for the treatment of advanced melanoma (Lifileucel) and synovial sarcoma (Afamitresgene autoleucel). To further expand the success of T cell products to solid tumors, promising preclinical studies suggest solutions to main obstacles, such as modular CAR T cells, targeting of two antigens simultaneously or generation of cytokine-secreting 4th generation CAR T cells.

P1, N=10, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2025 --> Nov 2026 | Trial primary completion date: Nov 2025 --> Nov 2026

This study demonstrated the feasibility of consistently generating sufficient TIL from HNSCC tumors. Results from this study suggest TIL cell therapy may serve as a potential treatment option for patients with HNSCC and support further development, including TIL cell therapy combined with immune checkpoint inhibitors or other agents or with other TIL products.

The FDA approval of afamitresgene autoleucel for advanced synovial sarcoma and the breakthrough designation of letetresgene autoleucel for myxoid/round cell liposarcoma signify a major turning point...Tumour infiltrating lymphocyte therapy, including lifileucel, is under investigation with checkpoint inhibitors or oncolytic agents to enhance efficacy and manage toxicity...Challenges include HLA restriction, tumour heterogeneity, and manufacturing complexity. Future strategies involving novel antigens, multi-targeting, and combinatorial regimens could broaden patient eligibility and improve therapeutic outcomes.

These findings demonstrate the feasibility of ex vivo TIL expansion from EC tumors. This study provides a rationale for the initiation of the phase II clinical trial IOV-END-201 (NCT06481592) to evaluate lifileucel in patients with advanced EC.

The treatment of therapy-resistant advanced melanoma using TILs (lifileucel) is currently not cost-effective in small, middle-income economies and is unlikely to become so in the near future.