Association of PD-L1 expression and gene expression profiling with clinical response to pembrolizumab in patients with advanced recurrent ovarian cancer: Results from the phase II KEYNOTE-100 study (2018)

Background: KEYNOTE-100 (NCT02674061) showed pembrolizumab (pembro) has clinical activity in patients (pts) with advanced ovarian cancer (AOC), and PD-L1 expression (combined positive score [CPS] ≥10) was associated with response. Other biomarkers possibly associated with response were evaluated. Methods: Key inclusion criteria included epithelial ovarian, fallopian tube, or primary peritoneal cancer, confirmed recurrence following front-line platinum-based therapy, ECOG PS 0/1, and tumor sample. Pts received pembro 200 mg Q3W IV for 2 y or until progression, death, unacceptable toxicity, or consent withdrawal. Whole exome sequencing of paired tumor and normal samples determined homologous recombination deficiency genomic scar (HRD) and BRCA1/2 mutation status (BRCA) using standard algorithms. Associations of response with T-cell-inflamed 18-gene expression profile (T-cell-GEP) score, HRD, BRCA, and microsatellite instability-high (MSI-H) were evaluated. Results: T-cell-GEP, BRCA, and HRD data were available from the first 100 pts enrolled, while MSI-H was from the entire study population (n = 319). Among patients with T-cell-GEP, distribution of GEP scores was significantly higher in responders than nonresponders (1-sided p = 0.03 from Wilcoxon rank sum test; n = 83). 7/83 pts (8.4%) had a response. In pts with available PD-L1 CPS and GEP (n = 79; Spearman’s correlation ρ = 0.57), the area under the receiver characteristic curves for CPS and T-cell-GEP were numerically similar (0.73 vs 0.72, respectively). No statistically significant differences were observed with HRD values among responders and nonresponders (1-sided p = 0.29; n = 71). No association between BRCA status (n = 11 mutant; n = 60 wild type) and response was observed (1-sided p = 0.65). 6/71 pts (8.5%) in this population had a response. Of 319 paired samples tested for MSI-H, all were MSS. Conclusions: In addition to PD-L1 CPS, T-cell-GEP was associated with a response to pembro monotherapy for treatment of AOC in a single-arm setting, while HRD biomarkers (HRD, BRCA) were not found to be associated with response. Clinical trial identification: NCT02674061; Release date, February 25, 2016. Editorial acknowledgement: Medical writing assistance was provided by Christine McCrary Sisk, an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and by Matthew Grzywacz, ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Legal entity responsible for the study: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Funding: Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Disclosure: J.A. Ledermann: Honoraria or consultation fees: Pfizer, AstraZeneca, Clovis, MSD, Roche; Company-sponsored speaker's bureau: AstraZeneca. R. Shapira-Frommer: Advisory board member: Clovis, Novartis; Honoraria: MSD, BMS, Novartis, Roche, AstraZeneca; Travel expenses: MSD, BMS, AstraZeneca. I. Vergote: Consultant/advisory board: Eisai, MSD Belgium, Roche, Genmab, Pharma Mar, AstraZeneca, Eli Lilly, Amgen, Pfizer, Novartis, Bayer; Contracted research: Oncoinvent, Genmab; Grants: Amgen, Roche; Travel: Takeda, Pharma Mar, Genmab, Roche, AstraZeneca. F. Raspagliesi: Advisory board member: Roche, AstraZeneca; Speaker's bureau: Roche, AstraZeneca. G.S. Sonke: Research funding: AstraZeneca, Merck, Novartis, Roche. J. Sehouli: Advisory board: Clovis, Tesaro, AstraZeneca, Roche, Lilly, Pfizer, Merci, Pharmamar, Bayer; Research: AstraZeneca, Lilly, Bayer, Medac, Tesaro; Honoraria: Tesaro, AstraZeneca, Pharmamar, Roche; Travel: Tesaro, AstraZeneca, Pharmamar, Roche. N. Colombo: Advisory board member: Roche, Pharmamar, Clovis, Tesaro, Astra Zeneca, Pfizer, Biocad; Speaker's bureau: AstraZeneca, Roche, Pharmamar, Tesaro. A. González-Martín: Advisory board member: Tesaro, Roche, AstraZeneca, Clovis, Pharmamar; Speakers' bureau: Tesaro, Roche, AstraZeneca, Pharmamar; Travel expenses, accomodations: AstraZeneca, Roche, Tesaro. A. Oaknin: Advisory boards: Roche, AstraZeneca, PharmaMar, Clovis Oncology, Tesaro; Support for travel or accommodation: Roche, AstraZeneca, PharmaMar. V. Rudaitis: P.I. for Merck Co.; Honararia: AstraZeneca, GSK, Orivas; Travel expenses, accommodations: Roche. R. Cristescu, J. Kobie: Employee of Merck & Co. Inc. J. Ruman: Employee of Merck Research Laboratories. U.A. Matulonis: Advisory board member: Merck, Immunogen, Fujifilm, 2X Oncology, Geneos, Mersana. All other authors have declared no conflicts of interest.