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

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.

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Publication Details

Journal
Nature Communications
Published
2025-02-05
DOI
https://doi.org/10.1038/s41467-025-56482-w
Citations
16
Primary Topic
Virus-based gene therapy research
Type
article
Field-Weighted Citation Impact
29.08

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article

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

Matthew Stephen Block, Santeri A. Pakola, Katja Välimäki, Saru Basnet et al.
16 citations
Nature Communications
Virus-based gene therapy research
29.08
article

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

Matthew Stephen Block, Santeri A. Pakola, Katja Välimäki, Saru Basnet, Elise Jirovec, Jorma Sormunen, Tatiana V. Kudling, Riikka Havunen, Teijo Pellinen, Victor Arias, James H.A. Clubb, John Goldfinch, Michael Chisamore, Claudia Kistler, Aino Kalervo, Lyna Haybout, Julia W. Cohen, Dafne C.A. Quixabeira, Akseli Hemminki, Juha Kononen, Suvi Sorsa, Tuomo Alanko, Annukka Pasanen, Annabrita Hemmes, João M. Santos, Daniel A. Adamo, Víctor Cervera-Carrascón, Susan Ramadan, Susanna Grönberg-Vähä-Koskela, Johanna Mäenpää, Mirte van der Heijden, Nea Ojala, Sanae Zahraoui, Sini Raatikainen
article en
16 citations

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.

Nature CommunicationsVol. 16(1)
Merck & Co., Inc., Rahway, NJ, USA (United States) (US), University of Helsinki (FI), Tampere University (FI), Helsinki University Hospital (FI), Biocenter Finland (FI), Ministry of Finance (FI), Mayo Clinic in Arizona (US), Institute for Molecular Medicine Finland (FI), Docrates Cancer Center (FI), Hospital District of Helsinki and Uusimaa (FI)
U.S. Department of Defense, Suomen Kulttuurirahasto, Punainen Risti Veripalvelu, Jane ja Aatos Erkon Säätiö, Syöpäsäätiö, Biocenter Finland, Helsinki Institute of Life Science, Helsingin Yliopisto
Good health and well-being
Openalex Percentile: Top 0%
Virus-based gene therapy research
29.08
DOIOpen Access PDFOpenAlex
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