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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2025-02-01
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| author | 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 |
| author_facet | 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 |
| author_sort | Matthew Stephen Block |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-423ec24658f241b9a0ebd40284ad5df9 |
| institution | Kabale University |
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| publishDate | 2025-02-01 |
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| spelling | doaj-art-423ec24658f241b9a0ebd40284ad5df92025-02-09T12:45:22ZengNature PortfolioNature Communications2041-17232025-02-0116111410.1038/s41467-025-56482-wThe oncolytic adenovirus TILT-123 with pembrolizumab in platinum resistant or refractory ovarian cancer: the phase 1a PROTA trialMatthew Stephen Block0James Hugo Armstrong Clubb1Johanna Mäenpää2Santeri Pakola3Dafne Carolina Alves Quixabeira4Tatiana Kudling5Elise Jirovec6Lyna Haybout7Mirte van der Heijden8Sanae Zahraoui9Susanna Grönberg-Vähä-Koskela10Sini Raatikainen11Victor Arias12Saru Basnet13Nea Ojala14Teijo Pellinen15Annabrita Hemmes16Katja Välimäki17Annukka Pasanen18Tuomo Alanko19Daniel Adamo20Susan Ramadan21Jorma Sormunen22Juha Kononen23Julia Wanda Cohen24Michael Jon Chisamore25John Goldfinch26Suvi Sorsa27Riikka Havunen28Claudia Kistler29Aino Kalervo30Víctor Cervera-Carrascon31João Manuel dos Santos32Akseli Hemminki33Mayo Clinic Cancer CenterTILT Biotherapeutics LtdDocrates Cancer CenterCancer Gene Therapy Group, Translational Immunology Research Program, University of HelsinkiTILT Biotherapeutics LtdTILT Biotherapeutics LtdTILT Biotherapeutics LtdTILT Biotherapeutics LtdCancer Gene Therapy Group, Translational Immunology Research Program, University of HelsinkiTILT Biotherapeutics LtdCancer Gene Therapy Group, Translational Immunology Research Program, University of HelsinkiTILT Biotherapeutics LtdCancer Gene Therapy Group, Translational Immunology Research Program, University of HelsinkiCancer Gene Therapy Group, Translational Immunology Research Program, University of HelsinkiCancer Gene Therapy Group, Translational Immunology Research Program, University of HelsinkiDigital Microscopy and Molecular Pathology Unit, Institute for Molecular Medicine FinlandDigital Microscopy and Molecular Pathology Unit, Institute for Molecular Medicine FinlandDigital Microscopy and Molecular Pathology Unit, Institute for Molecular Medicine FinlandDepartment of Pathology, University of Helsinki and Helsinki University HospitalDocrates Cancer CenterMayo Clinic Cancer CenterDocrates Cancer CenterDocrates Cancer CenterDocrates Cancer CenterMerck & Co. Inc.Merck & Co. Inc.TILT Biotherapeutics LtdTILT Biotherapeutics LtdTILT Biotherapeutics LtdTILT Biotherapeutics LtdTILT Biotherapeutics LtdTILT Biotherapeutics LtdTILT Biotherapeutics LtdTILT Biotherapeutics LtdAbstract 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.https://doi.org/10.1038/s41467-025-56482-w |
| spellingShingle | 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 The oncolytic adenovirus TILT-123 with pembrolizumab in platinum resistant or refractory ovarian cancer: the phase 1a PROTA trial Nature Communications |
| title | The oncolytic adenovirus TILT-123 with pembrolizumab in platinum resistant or refractory ovarian cancer: the phase 1a PROTA trial |
| title_full | The oncolytic adenovirus TILT-123 with pembrolizumab in platinum resistant or refractory ovarian cancer: the phase 1a PROTA trial |
| title_fullStr | The oncolytic adenovirus TILT-123 with pembrolizumab in platinum resistant or refractory ovarian cancer: the phase 1a PROTA trial |
| title_full_unstemmed | The oncolytic adenovirus TILT-123 with pembrolizumab in platinum resistant or refractory ovarian cancer: the phase 1a PROTA trial |
| title_short | The oncolytic adenovirus TILT-123 with pembrolizumab in platinum resistant or refractory ovarian cancer: the phase 1a PROTA trial |
| title_sort | oncolytic adenovirus tilt 123 with pembrolizumab in platinum resistant or refractory ovarian cancer the phase 1a prota trial |
| url | https://doi.org/10.1038/s41467-025-56482-w |
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