Pembrolizumab (pembro) plus low-dose ipilimumab (ipi) for patients (pts) with advanced renal cell carcinoma (RCC): Phase 1 KEYNOTE-029 study.

Abstract

510 Background: The CTLA-4 antibody ipi and the PD-1 antibody pembro have demonstrated efficacy in pts with advanced malignancies. While these immune checkpoint inhibitors have shown robust activity as monotherapy, combination therapy may further improve outcomes. KEYNOTE-029 (NCT02089685) is a phase 1/2 study designed to assess the safety and efficacy of pembro + ipi or pegylated interferon alfa-2b (IFN-α) in pts with advanced melanoma or RCC. Here we report data from the phase 1 portion of the study in pts with RCC treated with pembro + ipi. Methods: Pts ≥18 years with advanced/unresectable or metastatic clear cell RCC who received ≥1 prior therapy for metastatic disease, had ≥1 measurable lesion per RECIST v1.1, and ECOG PS 0-1 were enrolled. Pts received pembro 2 mg/kg Q3W + low-dose ipi (1 mg/kg Q3W for 4 doses) until disease progression, unacceptable toxicity, investigator/patient decision, or 2 years of pembro treatment. AEs were monitored throughout treatment and for 30 days thereafter and graded per NCI CTCAE v4.0. Primary end point was safety; primary efficacy end point was ORR assessed per RECIST v1.1 by independent central imaging vendor review. Results: As of the March 17, 2016, data cutoff, 10 pts with RCC received pembro + low-dose ipi. 60% were male, 70% were white, median age was 61 years (range, 48-70 years), 40% received 2 prior lines of therapy, and 40% received prior immunotherapy. With a median follow-up of 17.4 months (0.9-23.5 months), 70% of pts experienced treatment-related AEs (TRAEs) of any grade, most commonly fatigue (30%); and 50% experienced grade 3/4 TRAEs, most commonly increased lipase (20%). 50% of pts discontinued pembro because of TRAEs, most commonly increased lipase (40%). There were no treatment-related deaths. ORR was 20% (2 partial responses); median duration of response was not reached (14.1+-17.1 months+). An additional 3 pts had stable disease; disease control rate was 50%. Conclusions: The combination of pembro + low-dose ipi for 4 doses, followed by pembro monotherapy, demonstrates a manageable toxicity profile and preliminary antitumor activity in pts with advanced RCC. Clinical trial information: NCT02089685.