Pembrolizumab (pembro) plus ipilimumab (ipi) for advanced melanoma: Results of the KEYNOTE-029 expansion cohort.

Abstract

9506 Background: Pembro (MK-3475), an anti–PD-1 antibody that prevents PD-1 from binding to its ligands, PD-L1 and PD-L2, is approved in several countries for treating advanced melanoma. In KEYNOTE-006, pembro showed superior OS over the anti–CTLA-4 inhibitor ipi. In a phase 3 trial, combination therapy with reduced-dose nivolumab (anti–PD-1) and standard-dose ipi showed higher ORR and longer PFS than either checkpoint inhibitor alone but was associated with increased toxicity. Preliminary data from the phase 1 KEYNOTE-029 study (NCT02089685) suggested that standard-dose pembro + reduced-dose ipi was safe and provided robust antitumor activity. Here, we present data from a larger population of patients (pts) treated with pembro + ipi in the KEYNOTE-029 expansion cohort. Methods: Eligible pts had advanced melanoma, ECOG PS 0-1, no active brain metastases, and no prior immune checkpoint inhibitor therapy. Pts received pembro 2 mg/kg Q3W + ipi 1 mg/kg Q3W for 4 doses, then pembro 2 mg/kg Q3W until intolerable toxicity, progression, or 2 y. Response was assessed by RECIST v1.1 at wk 12, every 6 wk until wk 30, then every 12 wk thereafter. Results: Of 153 pts enrolled in the expansion, 107 had ≥18 wk of follow-up (median 6.4 mo, range 4.3-9.4) by the Oct 26, 2015, data cutoff and were eligible for analysis. 18% of pts had elevated LDH, 55% had stage M1c disease, 36% were BRAFV600mutant, 13% received ≥1 prior therapy, and 12% received a prior BRAF ± MEK inhibitor; 84% had PD-L1–positive tumors (ie, ≥1% staining in tumor and adjacent immune cells). 79 pts (74%) received all 4 ipi doses; 73 pts (68%) remained on pembro. 41 pts (38%) had ≥1 grade 3-4 drug-related AE (DRAE); 68% of these DRAEs resolved by data cutoff. DRAEs led to discontinuation of pembro and ipi in 9 pts (8%), ipi alone in 11 (10%), and pembro alone in 4 (4%); there were no treatment-related deaths. Immune-mediated AEs of any grade and grade 3-4 severity occurred in 57 (53%) and 21 (20%) pts. ORR by investigator review was 57%, with 5 (5%) CR and 56 (52%) PR; by central review, ORR was 51%, with 9% CR and 42% PR. Conclusions: Pembro 2 mg/kg in combination with 4 doses of ipi 1 mg/kg has a manageable toxicity profile and provides robust antitumor activity in pts with advanced melanoma. Clinical trial information: NCT02089685.