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

Author

Listed:
  • Matthew Stephen Block

    (Mayo Clinic Cancer Center)

  • James Hugo Armstrong Clubb

    (TILT Biotherapeutics Ltd
    University of Helsinki)

  • Johanna Mäenpää

    (Docrates Cancer Center
    Faculty of Medicine and Medical Technology)

  • Santeri Pakola

    (University of Helsinki)

  • Dafne Carolina Alves Quixabeira

    (TILT Biotherapeutics Ltd
    University of Helsinki)

  • Tatiana Kudling

    (TILT Biotherapeutics Ltd
    University of Helsinki)

  • Elise Jirovec

    (TILT Biotherapeutics Ltd
    University of Helsinki)

  • Lyna Haybout

    (TILT Biotherapeutics Ltd
    University of Helsinki)

  • 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
    University of Helsinki)

  • Riikka Havunen

    (TILT Biotherapeutics Ltd
    University of Helsinki)

  • Claudia Kistler

    (TILT Biotherapeutics Ltd)

  • Aino Kalervo

    (TILT Biotherapeutics Ltd)

  • Víctor Cervera-Carrascon

    (TILT Biotherapeutics Ltd
    University of Helsinki)

  • João Manuel Santos

    (TILT Biotherapeutics Ltd
    University of Helsinki)

  • Akseli Hemminki

    (TILT Biotherapeutics Ltd
    University of Helsinki
    Helsinki University Hospital)

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.

Suggested Citation

  • Matthew Stephen Block & James Hugo Armstrong Clubb & Johanna Mäenpää & Santeri Pakola & Dafne Carolina Alves Quixabeira & Tatiana Kudling & Elise Jirovec & Lyna Haybout & Mirte Heijden & Sanae Zahraou, 2025. "The oncolytic adenovirus TILT-123 with pembrolizumab in platinum resistant or refractory ovarian cancer: the phase 1a PROTA trial," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56482-w
    DOI: 10.1038/s41467-025-56482-w
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