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

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

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 o...

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Main Authors: Matthew Stephen Block, James Hugo Armstrong Clubb, Johanna Mäenpää, Santeri Pakola, Dafne Carolina Alves Quixabeira, Tatiana Kudling, Elise Jirovec, Lyna Haybout, Mirte van der 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 dos Santos, Akseli Hemminki
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-56482-w
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Summary: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.
ISSN:2041-1723

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