KEYNOTE-427 (NCT02853344) is a single-arm, open-label, phase 2 study of pembro monotherapy in patients (pts) with advanced clear cell RCC (cohort A) and nccRCC (cohort B). Updated cohort B results with additional follow-up are presented.
165 pts with histologically confirmed nccRCC, no prior systemic therapy, and measurable disease (RECIST v1.1) enrolled. Pts received pembro 200 mg IV Q3W for 35 cycles (∼2 y) or until progressive disease, unacceptable toxicity, or withdrawal. Primary end point: objective response rate (ORR, RECIST v1.1 by blinded independent central review). Additional end points: duration of response (DOR), PFS, OS, data by sarcomatoid differentiation, histology, and PD-L1 expression (combined positive score [CPS] ≥1 for PD-L1+).
Histology by central pathology review: papillary 72% (n = 118), chromophobe 13% (n = 21), unclassified 16% (n = 26); 62% were PD-L1+. Median follow-up: 15.0 mo (range, 0.9-25.4). Overall ORR was 26.1% (95% CI, 19.5-33.5; 10 [6.1%] CR, 33 [20.0%] PR) and median (range) DOR was 15.3 mo (2.8-21.0+). For responders, 57.3% had a response ≥12 mo. 12-mo PFS and OS rates were 24.7% and 73.7%, respectively. ORR (95% CI) was 28.0% (20.1-37.0) in papillary, 9.5% (1.2-30.4) in chromophobe, and 30.8% (14.3-51.8) in unclassified nccRCC; for responders, 55.4%, 50.0%, and 71.4% in the papillary, chromophobe and unclassified groups had a response ≥12 mo. Median (range) DOR was not reached in the unclassified and was 15.3 mo (2.8-21.0+) for the papillary group. ORR (95% CI) was 42.1% (26.3-59.2) for pts with sarcomatoid differentiation (n = 38). ORR (95% CI) in pts with CPS≥1 and CPS<1 was 35.3% (26.1-45.4) and 10.3% (3.9-21.2), respectively. Grade 3-5 treatment-related adverse events (TRAEs) occurred in 14% of pts. 7 pts died of AEs, 2 of TRAEs (pneumonia and cardiac arrest).
Single-agent pembro continued to show encouraging antitumor activity in nccRCC, especially with papillary or unclassified histology and CPS≥1. Safety profile of pembro was as expected.