4311 - Initial results from a phase 3b/4 study evaluating two dosing regimens of nivolumab (NIVO) in combination with ipilimumab (IPI) in patients with advanced melanoma (CheckMate 511)

Background

Combined inhibition of PD-1 and CTLA-4 with NIVO and IPI has demonstrated increased antitumor activity across several tumor types at various doses. In melanoma (MEL), NIVO 1 mg/kg plus IPI 3 mg/kg (NIVO1+IPI3) is the approved dose based on the CheckMate 067 trial, in which NIVO1+IPI3 and NIVO 3 mg/kg showed a higher objective response rate (ORR), longer progression-free survival (PFS), and improved overall survival (OS) vs IPI alone in patients (pts) with treatment-naive advanced MEL. CheckMate 511 was conducted to determine if NIVO 3 mg/kg plus IPI 1 mg/kg (NIVO3+IPI1) improves the safety profile of the combination.

Methods

Eligible pts were ≥18 years of age with unresectable stage III or IV MEL, an ECOG performance status of 0 or 1, no prior systemic therapy, and measurable disease by RECIST v1.1. Pts (N=360) were randomized 1:1 to NIVO3+IPI1 or NIVO1+IPI3 Q3W x 4; after combination therapy, pts in both groups received NIVO at 480 mg Q4W until progression or unacceptable toxicity. The primary objective was to compare the incidence of treatment-related grade 3-5 adverse events (AEs) between groups. Secondary objectives included descriptive analyses of efficacy endpoints, including ORR, PFS, and OS.

Results

At a minimum follow-up of ~12 months, the incidence of treatment-related grade 3-5 AEs among treated pts was significantly lower with NIVO3+IPI1 vs NIVO1+IPI3 (Table). One treatment-related grade 5 AE was reported in the NIVO3+IPI1 group and none in the NIVO1+IPI3 group. While ORR numerically favored NIVO1+IPI3, there were no significant differences in ORR, PFS or OS (Table).

Conclusions

CheckMate 511 met its primary endpoint, demonstrating a significantly lower incidence of treatment-related grade 3-5 AEs with NIVO3+IPI1 compared with NIVO1+IPI3 in MEL. Similar efficacy outcomes were observed between the two groups; however, longer follow-up may help to better evaluate outcomes.

Clinical trial identification

ClinicalTrials.gov, NCT02714218

Editorial Acknowledgement

Professional medical writing and editorial assistance were provided by Ward A. Pedersen, PhD, and Cara Hunsberger at StemScientific, an Ashfield Company, funded by Bristol-Myers Squibb.