Abstract 1048: Genomic analysis of patients with relapsed ovarian cancer enrolled in a phase II trial of nivolumab and bevacizumab

Abstract

Abstract We analyzed genomic alterations in patients with relapsed ovarian cancer treated with combined nivolumab and bevacizumab in a phase II clinical trial, in order to identify potential biomarkers of response. Thirty-eight patients were treated with nivolumab and bevacizumab and the previously reported overall response rate was 28.9% (Liu et al, JAMA Oncology, 2019). Formalin-fixed paraffin-embedded patient tumor samples (acquired pre-treatment) underwent whole-exome sequencing, followed by quality control filtering and analysis of mutations, insertions/deletions, copy-number alterations, and mutational signatures using established methods. Differences in genomic event rates were assessed between response groups, as defined by presence or absence of objective response or clinical benefit. We describe the genomic alterations in all patients treated with nivolumab and bevacizumab, including several long-term responders with treatment duration >24 months. The observed alterations in the patient cohort reflected known patterns of common mutations (e.g. TP53) and copy-number alterations (e.g. MYC amplification) in ovarian cancer. Within the limits of sample size, no significant differences in frequency of specific mutations were observed between response groups, with the possible exception of mutations in SETD1B, a histone methyltransferase, which were more frequent in the subset of patients lacking clinical benefit. BRCA1/2 mutation rate was similar between groups. Tumor mutational burden was not significantly different between groups. Initial exploratory analysis for copy-number alterations did not reveal genes with differential copy-number alterations between the response groups, and further analyses of copy-number alterations and mutational signatures are in progress. In summary, we describe genomic biomarker analysis from tumors of patients with relapsed ovarian cancer receiving treatment with nivolumab and bevacizumab. Taken together, we did not identify genomic alterations that clearly distinguish responding and non-responding patients in the data evaluated to date. Analysis of targeted RNA-sequencing data is planned as a next step. Further studies are needed to identify genomic or transcriptomic biomarkers of responses to checkpoint blockade and anti-angiogenic therapy in ovarian cancer. Citation Format: Elizabeth H. Stover, Svitlana Tyekucheva, Yiwen Liu, Jennifer D. Curtis, Richard T. Penson, Joyce F. Liu. Genomic analysis of patients with relapsed ovarian cancer enrolled in a phase II trial of nivolumab and bevacizumab [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1048.