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)

Int J Gynecol Cancer. 2020 Dec;30(12):1997-2001. doi: 10.1136/ijgc-2020-001572. Epub 2020 Jun 30.

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.

Keywords: ovarian cancer.

Publication types

  • Clinical Trial Protocol
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab / administration & dosage
  • Carcinoma, Ovarian Epithelial / drug therapy*
  • Clinical Trials, Phase III as Topic
  • Doxorubicin / administration & dosage
  • Doxorubicin / analogs & derivatives
  • Female
  • Humans
  • Neoplasm Recurrence, Local / drug therapy*
  • Ovarian Neoplasms / drug therapy*
  • Paclitaxel / administration & dosage
  • Polyethylene Glycols / administration & dosage
  • Progression-Free Survival
  • Randomized Controlled Trials as Topic

Substances

  • Antibodies, Monoclonal, Humanized
  • liposomal doxorubicin
  • Bevacizumab
  • Polyethylene Glycols
  • atezolizumab
  • Doxorubicin
  • Paclitaxel

Associated data

  • ClinicalTrials.gov/NCT03353831