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Clinical Trial
. 2025 Mar 18;6(3):102016.
doi: 10.1016/j.xcrm.2025.102016.

Safety and efficacy of combined treatment with tumor-infiltrating lymphocytes and oncolytic adenovirus TILT-123 in metastatic melanoma

Tine J Monberg  1 , Santeri A Pakola  2 , Benedetta Albieri  1 , Eva Ellebaek  1 , Marco Donia  1 , Rikke L Eefsen  1 , Troels H Borch  1 , Tatiana V Kudling  2 , Torben Lorentzen  3 , Helle W Hendel  4 , Cecilie Vestergaard  1 , Cathrine Lorentzen  1 , Rikke B Holmstroem  1 , Victor Arias  2 , Amir Khammari  5 , Claudia Kistler  6 , João M Santos  7 , James H A Clubb  7 , Lyna Haybout  7 , Marie C W Westergaard  1 , Özcan Met  8 , Dafne C A Quixabeira  7 , Elise Jirovec  2 , Riikka Havunen  7 , Suvi Sorsa  6 , Victor Cervera-Carrascon  7 , Brigitte Dreno  5 , Akseli Hemminki  9 , Inge Marie Svane  10
Affiliations
Clinical Trial

Safety and efficacy of combined treatment with tumor-infiltrating lymphocytes and oncolytic adenovirus TILT-123 in metastatic melanoma

Tine J Monberg et al. Cell Rep Med. .

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.

Keywords: TIL therapy; cancer immunotherapy; combination immunotherapy; cutaneous melanoma; mucosal melanoma; oncolytic virus therapy; tumor-infiltrating lymphocytes; uveal melanoma.

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Conflict of interest statement

Declaration of interests T.J.M. has been a co-investigator in a trial from TILT Biotherapeutics. E.E. has received personal payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Novartis, Merck, Bristol Myers Squibb, and Pierre Fabre. She has received support for attending meetings and/or travel from Pierre Fabre and Merck. M.D. is an advisor of Achilles Therapeutics and expert group member of Guidepoint LLC and AlphaSights. R.L.E. received institutional drug funding from BMS to investigator-initiated trial. T.H.B. has received personal honoraria for lectures from Bristol Myers Squibb. C.K. is an employee and shareholder at TILT Biotherapeutics. J.M.S. is an employee and stocks/share holder at TILT Biotherapeutics. He received a research grant from TILT Biotherapeutics. He is a co-inventor of patent applications for TILT Biotherapeutics. He received personal payment for consultancy for TILT Biotherapeutics. J.H.A.C. is an employee and shareholder at TILT Biotherapeutics. L.H. is an employee and option holder at TILT Biotherapeutics. D.C.A.Q. is an employee and shareholder at TILT Biotherapeutics. R.H. is an employee at TILT Biotherapeutics. S.S. is an employee and option holder at TILT Biotherapeutics. V.C.-C. is an employee and shareholder at TILT Biotherapeutics. A.H. is a shareholder in Circio Holding ASA and an employee and shareholder at TILT Biotherapeutics Oy. I.M.S. has received personal payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, advisory board, or educational events from Bristol Myers Squibb, Instil Bio, Mendus, MSD, Novartis, Sanofi, and Takeda. She has stocks/shares in IO Biotech. She has received research grants from Adaptimmune, Asgard Therapeutics, Enara Bio, IO Biotech, Lytix Biopharma, and TILT Biotherapeutics. She has been principal investigator in trials from BMS, Immunocore, Lytix Biopharma, MSD, Novartis, Roche, and TILT Biotherapeutics. The TILT technology is patented by the company TILT Biotherapeutics.

Figures

None
Graphical abstract
Figure 1
Figure 1
TILT-T215 CONSORT diagram
Figure 2
Figure 2
Efficacy of the treatment (A) Best overall response (BOR). Percentage change in tumor burden was evaluated by RECIST 1.1. CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease. CI, 95% confidence interval. (B) Progression-free survival, n = 17. Median PFS (mPFS) = 78 days.
Figure 3
Figure 3
Swimmer plot Swimmer plot illustrating time to progressing or data cutoff for each patient separately. Colors indicate best overall response on day 78 or later. Stars indicate patients who have died. Triangles indicate patients still alive.
Figure 4
Figure 4
Overall survival Median overall survival (mOS) = 620 days.
Figure 5
Figure 5
PET response day 36 and 78 PMR, partial metabolic response; MMR, minor metabolic response; SMD, stable metabolic disease; PMD, progressive metabolic disease; CI, 95% confidence interval. (A) Percentage change in SUVmax evaluated on day 78. (B) Percentage change in SUVmax evaluated on day 36.
See this image and copyright information in PMC

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