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Atezolizumab in combination with bevacizumab and chemotherapy versus bevacizumab and chemotherapy in recurrent ovarian cancer – a randomized phase III trial (AGO-OVAR 2.29/ENGOT-ov34)
  1. Philipp Harter1,
  2. Patricia Pautier2,
  3. Els Van Nieuwenhuysen3,
  4. Alexander Reuss4,
  5. Andres Redondo5,
  6. Kristina Lindemann6,
  7. Christian Kurzeder7,
  8. Edgar Petru8,
  9. Florian Heitz1,
  10. Jalid Sehouli9,
  11. Nikolaus Degregorio10,
  12. Pauline Wimberger11,
  13. Alexander Burges12,
  14. Nadin Cron13,
  15. Jonathan Ledermann14,
  16. Domenica Lorusso15,
  17. Xavier Paoletti16 and
  18. Frederik Marme17
  1. 1Gynecology and Gynecologic Oncology, AGO & Ev. Kliniken Essen-Mitte, Essen, Germany
  2. 2GINECO & Gustave Roussy, Villejuif, France
  3. 3Gynecological Oncology, BGOG & University Hospitals Leuven, Leuven, Belgium
  4. 4Coordinating Centre for Clinical Trials, AGO & Philipps-University, Marburg, Germany
  5. 5IdiPaz, GEICO & Hospital Universitario La Paz, Madrid, Spain
  6. 6NSGO & Oslo University Hospital, Unversity of Oslo, Oslo, Norway
  7. 7SAKK & University Hospital of Basel, Basel, Switzerland
  8. 8AGO-Austria & Graz University, Graz, Austria
  9. 9Department of Gynecology with Center for Oncological Surgery, Campus Virchow Klinikum, AGO & Charité Berlin, Berlin, Germany
  10. 10AGO & University Ulm, Ulm, Germany
  11. 11Gyncology and Obstetrics, AGO & TU Dresden, Dresden, Germany
  12. 12AGO & LMU Munich, Munchen, Bayern, Germany
  13. 13AGO, Essen, Germany
  14. 14UCL Cancer Institute, University College, London, UK
  15. 15Policlinico Gemelli, Rome, Italy
  16. 16Institute Curie, Paris, France
  17. 17AGO & University Mannheim, Mannheim, Germany
  1. Correspondence to Dr Philipp Harter, Gynecology and Gynecologic Oncology, AGO & Ev. Kliniken Essen-Mitte, Essen 45136, Germany; p.harter{at}gmx.de

Abstract

Background Improvement in clinical outcomes of patients with platinum-resistant disease is an unmet medical need and trials in this population are urgently needed. Checkpoint-inhibitors have already shown activity in multiple other tumor entities and ovarian cancer, especially in the combination with anti-angiogenic treatment.

Primary objective To test if the activity of non-platinum-based chemotherapy and bevacizumab could be improved by the addition of atezolizumab.

Study hypothesis The addition of atezolizumab to standard non-platinum combination of chemotherapy and bevacizumab improves median overall survival from 15 to 20 months.

Trial design Patients are randomized to chemotherapy (paclitaxel weekly or pegylated liposomal doxorubicin) + bevacizumab + placebo vs chemotherapy + bevacizumab + atezolizumab. Stratification factors are: number of prior lines, planned type of chemotherapy, prior use of bevacizumab, and tumor programmed death-ligand 1 (PD-L1) status.

Major inclusion/exclusion criteria Recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer with up to three prior therapies and a treatment-free interval after platinum of less than 6 months. Patients with three prior lines of chemotherapy are eligible irrespective of the platinum free-interval. A de novo tumor tissue sample biopsy for determination of PD-L1 status prior to randomization for stratification is mandatory. Major exclusion criteria consider bevacizumab-specific and immunotherapy-specific criteria.

Primary endpoint Overall survival and progression-free survival are co-primary endpoints.

Sample size It is planned to randomize 664 patients.

Trial registration NCT03353831.

  • ovarian cancer
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Footnotes

  • Contributors All co-auhtors are contributing to the trial, read and approved the manuscript.

  • Funding This study was funded by F. Hoffmann-La Roche.

  • Competing interests PH reports grants and personal fees from Astra Zeneca, grants and personal fees from Roche, personal fees from Sotio, grants and personal fees from Tesaro, personal fees from Stryker, personal fees from Zai Lab, personal fees from MSD, grants and personal fees from public funding (ASCO, DKH, DFG), personal fees from Clovis, personal fees from Immunogen, grants from GSK, grants from Boehringer Ingelheim, grants from Medac, grants from Genmab, outside the submitted work. PP reports personal fees from Roche Laboratory, other personal fees from MSD laboratory, other from Clovis Oncology, outside the submitted work. AR reports grants and personal fees from Pharmamar, personal fees from Lilly, personal fees from Novartis, personal fees from Amgen, personal fees from Astra Zeneca, personal fees from Tesaro, grants and personal fees from Roche, grants from Eisai, outside the submitted work. KL reports other personal fees from Astra Zeneca, other from GSK, outside the submitted work. CK reports personal fees and non-financial support from Roche, personal fees and non-financial support from Tessaro, personal fees and non-financial support from AstraZeneca, personal fees and non-financial support from Pfizer, personal fees and non-financial support from Pharmamar, personal fees from Lilly, personal fees from Genomic Health, outside the submitted work. EP reports personal fees from AGEA, personal fees from Amgen, personal fees from Astra Zeneca, personal fees from Angelini, personal fees from Celgene, personal fees from Eisai, personal fees from Eli Lilly, personal fees from GSK, personal fees from MSD, personal fees from Novartis, personal fees from Pharmamar, personal fees from Pfizer, personal fees from Roche, personal fees from Tesaro, personal fees from Clovis, personal fees from Daiichi Sankyo, outside the submitted work. FH reports non-financial support from NewOncology; personal fees from Roche, personal fees from AstraZeneca, from Clovis, personal fees from Tesaro, from PharmaMar, outside the submitted work. JS reports grants, non-financial support and other from Roche, grants, non-financial support, and other perdonal fees from PharmaMar, grants, non-financial support and other peredonal fees from Teasaro, grants, non-financial support and other personal fees from Clovis, grants, non-financial support and other peersonal fees from Astra Zeneca, grants and non-financial support from MSD, grants, non-financial support and other personal fees from Novocure, outside the submitted work. ND: Dr. de Gregorio reports personal fees from Roche, personal fees from GSK, personal fees from Pharmamar, personal fees from Astra Zeneca, personal fees from Clovis, personal fees from Ingress, from null, outside the submitted work. PW reports grants and personal fees from Amgen, personal fees from Astra Zeneca, personal fees from Clovis, personal fees from MSD, grants and personal fees from Novartis, personal fees from Pfizer, grants and personal fees from Roche, personal fees from Tesaro, personal fees from Eisai, personal fees from Pharmamar, personal fees from Teva, outside the submitted work. JL reports personal fees and other from Pfizer, grants and other from Merck/MSD, personal fees from Eisai, personal fees from Tesaro/GSK, grants and personal fees from AstraZeneca, personal fees from Artios, personal fees from Regeneron, outside the submitted work. DL reports grants, personal fees and non-financial support from Roche, grants, personal fees and non-financial support from Tesaro, grants and personal fees from Clovis, grants and personal fees from Merck, grants, personal fees and non-financial support from Pharmamar, personal fees from Immunogen, personal fees from Genmab, personal fees from Amgen, personal fees and non-financial support from Astra Zeneca, outside the submitted work. FM reports personal fees from Roche, personal fees from AstraZeneca, personal fees from Pfizer, personal fees from Tesaro, personal fees from Novartis, personal fees from Amgen, personal fees from PharmaMar, personal fees from GenomicHealth, personal fees from CureVac, personal fees from EISAI, outside the submitted work.

  • Patient consent for publication Not required.

  • Provenance and peer review Commissioned; externally peer reviewed.

  • Data availability statement There are no data in this work

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