Multicenter, double-blind, placebo-controlled trial of seviprotimut-L polyvalent melanoma vaccine in patients with post-resection melanoma at high risk of recurrence
Craig L. Slingluff, Karl D. Lewis, Robert Hans Ingemar Andtbacka, John Hyngstrom, Mohammed Milhem, Svetomir N. Markovic, Tawnya L. Bowles, Omid Hamid, Leonel F. Hernandez‐Aya, Joël Claveau, Sekwon Jang, Prejesh Philips, Shernan G. Holtan, Montaser Shaheen, Brendan D. Curti, William Schmidt, Marcus O. Butler, Juan Paramo, Jose Lutzky, Arvinda Padmanabhan, Sajeve Thomas, Daniel T. Milton, Andrew L. Pecora, Takami Sato, Eddy C. Hsueh, Suprith Badarinath, John A. Keech, Sujith Kalmadi, Pallavi Kumar, Robert Weber, Edward A. Levine, Adam C. Berger, Anna Bar, J. Thaddeus Beck, Jeffrey B. Travers, Catalin Mihalcioiu, Brian Gastman, Peter D. Beitsch, Suthee Rapisuwon, John A. Glaspy, Edward C. McCarron, Vinay Gupta, Deepti Behl, Brent A. Blumenstein, Joanna Peterkin
Abstract
BACKGROUND: Most patients with advanced melanomas relapse after checkpoint blockade therapy. Thus, immunotherapies are needed that can be applied safely early, in the adjuvant setting. Seviprotimut-L is a vaccine containing human melanoma antigens, plus alum. To assess the efficacy of seviprotimut-L, the Melanoma Antigen Vaccine Immunotherapy Study (MAVIS) was initiated as a three-part multicenter, double-blind, placebo-controlled phase III trial. Results from part B1 are reported here. METHODS: Patients with AJCC V.7 stage IIB-III cutaneous melanoma after resection were randomized 2:1, with stage stratification (IIB/C, IIIA, IIIB/C), to seviprotimut-L 40 mcg or placebo. Recurrence-free survival (RFS) was the primary endpoint. For an hypothesized HR of 0.625, one-sided alpha of 0.10, and power 80%, target enrollment was 325 patients. RESULTS: For randomized patients (n=347), arms were well-balanced, and treatment-emergent adverse events were similar for seviprotimut-L and placebo. For the primary intent-to-treat endpoint of RFS, the estimated HR was 0.881 (95% CI: 0.629 to 1.233), with stratified logrank p=0.46. However, estimated HRs were not uniform over the stage randomized strata, with HRs (95% CIs) for stages IIB/IIC, IIIA, IIIB/IIIC of 0.67 (95% CI: 0.37 to 1.19), 0.72 (95% CI: 0.35 to 1.50), and 1.19 (95% CI: 0.72 to 1.97), respectively. In the stage IIB/IIC stratum, the effect on RFS was greatest for patients <60 years old (HR=0.324 (95% CI: 0.121 to 0.864)) and those with ulcerated primary melanomas (HR=0.493 (95% CI: 0.255 to 0.952)). CONCLUSIONS: Seviprotimut-L is very well tolerated. Exploratory efficacy model estimation supports further study in stage IIB/IIC patients, especially younger patients and those with ulcerated melanomas. TRIAL REGISTRATION NUMBER: NCT01546571.