Final results from the KEYNOTE-100 trial of pembrolizumab in patients with advanced recurrent ovarian cancer.
Authors: Ursula A. Matulonis, Roni Shapira, Alessandro Santin, Alla Sergeevna Lisyanskaya, Sandro Pignata, Ignace Vergote, Francesco Raspagliesi, Gabe S. Sonke, Michael Birrer, Jalid Sehouli, Nicoletta Colombo, Antonio González-Martín, Ana Oaknin, P. B. Ottevanger, Vilius Rudaitis, Haiyan Wu, Stephen Michael Keefe, Karen Stein, Jonathan A. Ledermann
Journal: Journal of Clinical Oncology (2020)

6005 Background: Pembrolizumab (pembro) showed modest clinical activity in patients (pts) with recurrent advanced ovarian cancer (AOC) after a median follow-up of 16.9 mo in an interim analysis of KEYNOTE-100 (NCT02674061). We present the protocol-specified final analysis based on a data cutoff of 18-SEP-2019. Methods: Key eligibility criteria included epithelial ovarian, fallopian tube, or primary peritoneal cancer, confirmed recurrence following front-line platinum-based therapy, ECOG PS 0-1, and provision of a tumor sample for biomarker analysis. Pts in cohort A received ≤2 prior chemotherapy lines for recurrent AOC and had a platinum-free or treatment-free interval (PFI/TFI) of ≥3 to 12 mo. Pts in cohort B received 3-5 prior chemotherapy lines and had a PFI/TFI of ≥3 mo. Pts received pembro 200 mg Q3W for 2 yr or until progression, death, or unacceptable toxicity. Tumor imaging was performed every 9 wk for 1 yr and every 12 wk thereafter. Primary study endpoint was ORR per RECIST v1.1 by independent central review in both cohorts and by tumor PD-L1 expression using the combined positive score (CPS). Secondary endpoints included DOR, DCR (CR+PR+SD≥24 wk), PFS, OS, and safety. Results: 376 pts were enrolled and treated, 285 in cohort A and 91 in cohort B. Median age (range) was 61 (25 to 89) yr, 64.4% had ECOG PS 0, and 75.3% had high grade serous disease. In cohorts A and B, ORR (95% CI) was 8.1% (5.2, 11.9) and 9.9% (4.6, 17.9) in the total population, 6.9% (2.8, 13.8) and 10.2% (3.4, 22.2) in pts with CPS ≥1, and 11.6% (3.9, 25.1) and 18.2% (5.2, 40.3) in pts with CPS ≥10. Median DOR (range) was 8.3 (3.9 to 35.4+) mo in cohort A and 23.6 (3.3+ to 32.8+) mo in cohort B. DCR (95% CI) was 22.1% (17.4, 27.4) and 22.0% (14.0, 31.9). Median PFS was 2.1 mo in both cohorts. In cohorts A and B, median OS was 18.7 mo (17.0, 22.5) and 17.6 mo (13.3, 24.4) in the total population, 20.6 mo (15.2, 23.2) and 20.7 mo (13.6, 27.4) in pts with CPS ≥1, and 21.9 mo (12.9, 26.8) and 24.0 mo (14.5, NR) in pts with CPS ≥10. 73.7% of pts had treatment-related AEs and 20.2% were grades 3-4. There were 2 treatment-related deaths (Stevens-Johnson syndrome and hypoaldosteronism). Immune-mediated AEs occurred in 23.7% of pts. Conclusions: Pembro monotherapy was associated with modest antitumor activity in pts with recurrent AOC. There appeared to be a trend toward increased ORR with higher PD-L1 expression in both cohorts. Responses were durable and typically lasted ≥6 months. Median OS was 18.7 months overall, with a trend toward a longer OS with increasing PD-L1 expression in both cohorts. No new safety signals were identified. Clinical trial information: NCT02674061.