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).

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.

• Authors: Philipp Harter, Patricia Pautier, Els Van Nieuwenhuysen, Alexander Reuss, Andres Redondo, Kristina Lindemann, Christian Kurzeder, Edgar Petru, Florian Heitz, Jalid Sehouli, Nikolaus Degregorio, Pauline Wimberger, Alexander Burges, Nadin Cron, Jonathan Ledermann, Domenica Lorusso, Xavier Paoletti, Frederik Marme
• Journal: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society (Int J Gynecol Cancer) Vol. 30 Issue 12 Pg. 1997-2001 (12 2020) ISSN: 1525-1438 [Electronic] England
• PMID: 32606097 (Publication Type: Clinical Trial Protocol, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

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

Topics

• 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, 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