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<p>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 (<i>n</i> = 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月5日

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  • 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

摘要

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.