Pembrolizumab monotherapy as first-line therapy in advanced clear cell renal cell carcinoma (accRCC): Results from cohort A of KEYNOTE-427.

4500 Background: Programmed death-1 (PD-1) inhibitor–based combination therapy shows clinical benefit in first-line accRCC. However, data are limited on clinical impact of first-line PD-1 inhibitor monotherapy. KEYNOTE-427 (NCT02853344) is a single-arm, open-label, 2-cohort, phase 2 study that evaluates efficacy and safety of the PD-1 inhibitor pembrolizumab (pembro) as first-line monotherapy in accRCC and anccRCC. Results from the accRCC cohort (cohort A) are presented. Methods: Patients (pts) with histologically confirmed accRCC who received no prior systemic therapy were eligible. Additional key eligibility criteria included measurable disease (RECIST v1.1, independent central review ICR) and Karnofsky performance status ≥70%. Pembro 200 mg was administered intravenously Q3W for 2 y or until confirmed progressive disease, unacceptable toxicity, or pt decision to withdraw. Primary end point: objective response rate (ORR) per RECIST v1.1, ICR. Additional end points included duration of response, 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 were enrolled; 107 included in the efficacy analysis (opportunity for ≥1 postbaseline assessment). Median age (range) was 64 (29-87); 78% were male. 37.3%, 47.3%, and 15.5% of pts 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. ORR for pts with favorable, intermediate/poor risk IMDC was 27.5% and 37.3%, respectively. Median duration of response was not reached (range, 1.4+ to 8.2+). 73.6% of pts experienced a treatment-related adverse event (AE); most common (≥10%) were fatigue (23.6%), pruritus (21.8%), diarrhea (16.4%), rash (13.6%), and arthralgia (11.8%). 18.2% experienced a grade 3-5 treatment-related AE; 1 patient had grade 5 pneumonitis. Conclusions: Pembro monotherapy demonstrated promising efficacy and acceptable tolerability in pts with accRCC. Potential tissue-based biomarkers associated with response will be presented. Clinical trial information: NCT02853344.