Long-term efficacy of pembrolizumab (pembro; MK-3475) in a pooled analysis of 655 patients (pts) with advanced melanoma (MEL) enrolled in KEYNOTE-001.

Abstract

9005 Background: The anti–PD-1 antibody pembro is approved in the US for treating unresectable or metastatic MEL that progressed following ipilimumab (IPI) and, if BRAF V600 mutant, a BRAF inhibitor. Pembro has demonstrated robust antitumor activity and manageable toxicity in IPI- treated (IPI-T) and naive (IPI-N) pts. In KEYNOTE-002, pembro significantly prolonged PFS over chemotherapy in IPI-refractory MEL. Here we present long-term follow-up data for all pts with MEL enrolled in KEYNOTE-001 (NCT01295827). Methods: IPI-T and IPI-N pts received pembro 2 mg/kg every 3 weeks (Q3W), 10 mg/kg Q3W, or 10 mg/kg Q2W until unacceptable toxicity, disease progression, or investigator decision. Treatment could continue beyond initial radiographic progression in eligible pts. Response was assessed every 12 wks. Pts were followed for survival every 3 mo after discontinuation. Primary end point was ORR per RECIST v1.1 by central review; secondary end points included PFS, OS, and duration of response (DOR). Results: 655 pts enrolled: 342 IPI-T, 313 IPI-N. Medianfollow-up duration was 14.8 mo (range, 7.5-29). Median duration of exposure was 5.6 mo (range, 0.03-28.3). At the time of analysis, 217 (33%) pts remained on therapy. ORR was 34% (29% IPI-T, 38% IPI-N), with a 6% CR rate. Median time to response was 2.8 mo (range, 1.6-19.3). 80% of responses were ongoing at the time of analysis, and median DOR was not reached (range, 6+ to 98+ wk). Median PFS was 5.2 mo (95% CI 3.6-5.5) (IPI-T, 4.9 mo [3.0-5.5]; IPI-N, 5.4 mo [3.1-6.9]). PFS rates at 6 and 12 mo were 44% and 34% (41% and 32% IPI-T, 47% and 36% IPI-N). The 1-y OS rate was 67% (63% IPI-T, 71% IPI-N); the rate at 2 y was 50% (46% IPI-T, 53% IPI-N). Overall, 14% of pts experienced grade 3-4 treatment-related AEs, and there were no treatment-related deaths. In randomized cohorts, there were no significant differences in efficacy and safety between doses/schedules. Conclusions: Pembro provides robust and durable antitumor activity, promising long-term survival data, and a manageable safety profile in pts with IPI-T and IPI-N metastatic MEL. These results support the approved indication for pembro and its further exploration in other MEL populations. Clinical trial information: NCT01295827.