KEYNOTE-427 cohort A: Pembrolizumab monotherapy as first-line therapy in advanced clear cell renal cell carcinoma (ccRCC)

Abstract

Background: KEYNOTE-427 (NCT02853344) is a single-arm, open-label, 2-cohort, phase 2 study to evaluate efficacy and safety of the PD-1 inhibitor pembrolizumab (pembro) as first-line monotherapy in advanced ccRCC and non-ccRCC. Results from the ccRCC cohort (cohort A) are presented. Methods: Pembro 200 mg was administered intravenously Q3W for 2 y or until confirmed progressive disease, unacceptable toxicity, or patient (pt) decision to withdraw. Pts with histologically confirmed advanced ccRCC who had received no prior systemic therapy were eligible. Additional key eligibility criteria: measurable disease (RECIST v1.1, independent central review [ICR]) and Karnofsky performance status ≥70%. Primary end point: ORR per RECIST v1.1, by ICR. Additional end points: DOR, PFS, OS, safety, and biomarkers associated with response. Results: At data cutoff (Oct 6, 2017), median (range) follow-up was 7.2 (0.9-11.7) mo. 110 pts enrolled; 107 were included in efficacy analysis (opportunity for ≥1 postbaseline assessment). Treatment was ongoing for 64 (58.2%) pts. Median age (range) was 64 (29-87) years; 78% were male. 37.3%, 47.3%, and 15.5% had IMDC risk categories of favorable, intermediate, and poor, respectively. Confirmed ORR by ICR was 33.6% (n=36; 95% CI 24.8-43.4) with 1 complete response (0.9%) and 35 (32.7%) partial responses. 39 (36.4%) had stable disease. ORR for pts with favorable or intermediate/ poor risk IMDC was 27.5% and 37.3%, respectively. Median DOR was not reached (range 1.4+ to 8.2+ mo); 86.1% of responders had response ≥3 months. Median PFS was 6.9 (95% CI 5.1-NR) mo; PFS rate at 6mo was 53.6%. OS rates at 3 and 6mo were 97.2% and 92.4%, respectively. 73.6% of pts had a treatment-related adverse event (AE); most common (≥10%) were fatigue (23.6%), pruritus (21.8%), diarrhea (16.4%), rash (12.7%), and arthralgia (11.8%). 18.2% experienced a grade 3-5 treatment-related AE; 1 pt had grade 5 pneumonitis. Conclusions: Pembro monotherapy showed encouraging efficacy and acceptable tolerability in pts with advanced ccRCC. Updated analyses will be presented using additional follow-up data and outcomes by PDL-1 status and other relevant subgroups.