Safety and efficacy of combined treatment with tumor-infiltrating lymphocytes and oncolytic adenovirus TILT-123 in metastatic melanoma
Tine Monberg, Santeri A. Pakola, Benedetta Albieri, Eva Ellebæk, Marco Donia, Rikke Løvendahl Eefsen, Troels Holz Borch, Tatiana V. Kudling, Torben Lorentzen, Helle Westergren Hendel, Cecilie Vestergaard, Cathrine Lund Lorentzen, Rikke Boedker Holmstroem, Victor Arias, Amir Khammari, Claudia Kistler, João M. Santos, James H.A. Clubb, Lyna Haybout, Marie Christine Wulff Westergaard, Özcan Met, Dafne C.A. Quixabeira, Elise Jirovec, Riikka Havunen, Suvi Sorsa, Víctor Cervera-Carrascón, Brigitte Dréno, Akseli Hemminki, Inge Marie Svane
Abstract
Tumor-infiltrating lymphocytes (TILs) are effective in the treatment of metastatic melanoma (MM), but toxicity limits its application. TILT-123 (igrelimogene litadenorepvec) is an oncolytic adenovirus producing interleukin-2 (IL-2) and tumor necrosis factor (TNF) upon replication. In this phase 1 trial, 17 patients with metastatic checkpoint inhibitor-resistant melanoma are treated with TILT-123 and TILs without preconditioning chemotherapy or postconditioning IL-2. The treatment is safe and feasible. According to computed tomography (CT), the objective response rate is 11.7% (2/17) and disease control is observed in 35% (6/17), including a partial response lasting >8 months and a durable complete response in a mucosal melanoma patient. According to positron emission tomography (PET), disease control is observed in 7/15 (47%) with minor or partial responses in 4/15 (27%). In the initial TILT-123 monotherapy phase of the trial, disease control is observed in 6/17 (35%) and 10/16 (63%) in CT and PET, respectively. The study demonstrates good tolerability and preliminary efficacy.