The oncolytic adenovirus TILT-123 with pembrolizumab in platinum resistant or refractory ovarian cancer: the phase 1a PROTA trial

Matthew Stephen Block, James Hugo Armstrong Clubb, Johanna Mäenpää, Santeri Pakola, Dafne Carolina Alves Quixabeira, Tatiana Kudling, Elise Jirovec, Lyna Haybout, Mirte Heijden, Sanae Zahraoui, Susanna Grönberg-Vähä-Koskela, Sini Raatikainen, Victor Arias, Saru Basnet, Nea Ojala, Teijo Pellinen, Annabrita Hemmes, Katja Välimäki, Annukka Pasanen, Tuomo Alanko, Daniel Adamo, Susan Ramadan, Jorma Sormunen, Juha Kononen, Julia Wanda Cohen, Michael Jon Chisamore, John Goldfinch, Suvi Sorsa, Riikka Havunen, Claudia Kistler, Aino Kalervo, Víctor Cervera-Carrascon, João Manuel Santos and Akseli Hemminki ()
Additional contact information
Matthew Stephen Block: Mayo Clinic Cancer Center
James Hugo Armstrong Clubb: TILT Biotherapeutics Ltd
Johanna Mäenpää: Docrates Cancer Center
Santeri Pakola: University of Helsinki
Dafne Carolina Alves Quixabeira: TILT Biotherapeutics Ltd
Tatiana Kudling: TILT Biotherapeutics Ltd
Elise Jirovec: TILT Biotherapeutics Ltd
Lyna Haybout: TILT Biotherapeutics Ltd
Mirte Heijden: University of Helsinki
Sanae Zahraoui: TILT Biotherapeutics Ltd
Susanna Grönberg-Vähä-Koskela: University of Helsinki
Sini Raatikainen: TILT Biotherapeutics Ltd
Victor Arias: University of Helsinki
Saru Basnet: University of Helsinki
Nea Ojala: University of Helsinki
Teijo Pellinen: Institute for Molecular Medicine Finland
Annabrita Hemmes: Institute for Molecular Medicine Finland
Katja Välimäki: Institute for Molecular Medicine Finland
Annukka Pasanen: University of Helsinki and Helsinki University Hospital
Tuomo Alanko: Docrates Cancer Center
Daniel Adamo: Mayo Clinic Cancer Center
Susan Ramadan: Docrates Cancer Center
Jorma Sormunen: Docrates Cancer Center
Juha Kononen: Docrates Cancer Center
Julia Wanda Cohen: Merck & Co. Inc.
Michael Jon Chisamore: Merck & Co. Inc.
John Goldfinch: TILT Biotherapeutics Ltd
Suvi Sorsa: TILT Biotherapeutics Ltd
Riikka Havunen: TILT Biotherapeutics Ltd
Claudia Kistler: TILT Biotherapeutics Ltd
Aino Kalervo: TILT Biotherapeutics Ltd
Víctor Cervera-Carrascon: TILT Biotherapeutics Ltd
João Manuel Santos: TILT Biotherapeutics Ltd
Akseli Hemminki: TILT Biotherapeutics Ltd

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Immune checkpoint inhibitors have demonstrated modest efficacy as a monotherapy in ovarian cancer. Originally developed to improve efficacy of T-cell therapies such as immune checkpoint inhibitors and adoptive cell transfer, TILT-123 (Ad5/3-E2F-D24-hTNFα-IRES-hIL-2) is a serotype chimeric oncolytic adenovirus encoding tumor necrosis factor alpha and interleukin-2. Here we report results from phase 1a of PROTA, a single-arm, multicentre dose escalation trial with TILT-123 and pembrolizumab in female patients with platinum resistant or refractory ovarian cancer (NCT05271318). The primary endpoint was safety. Secondary endpoints included efficacy, tolerability, virus persistence and anti-viral immunity. Patients (n = 15) received intravenous and intraperitoneal and/or intratumoral injections of TILT-123 as well as intravenous pembrolizumab. Treatment was well tolerated, and no dose-limiting toxicities were observed. The most frequent adverse events were fever (40%), fatigue (40%) and nausea (40%). Disease control was achieved in 64% of evaluable patients (9/14). Median progression-free survival and overall survival were 98 and 190 days respectively. Clinical responses were associated with higher serum anti-adenovirus neutralizing antibody titer at baseline and post-treatment. The phase 1b investigating TILT-123, pembrolizumab and PEGylated liposomal doxorubicin in a similar patient population is underway.

Date: 2025
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DOI: 10.1038/s41467-025-56482-w

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