RT Journal Article SR Electronic T1 Multicenter, double-blind, placebo-controlled trial of seviprotimut-L polyvalent melanoma vaccine in patients with post-resection melanoma at high risk of recurrence JF Journal for ImmunoTherapy of Cancer JO J Immunother Cancer FD BMJ Publishing Group Ltd SP e003272 DO 10.1136/jitc-2021-003272 VO 9 IS 10 A1 Craig L Slingluff A1 Karl D Lewis A1 Robert Andtbacka A1 John Hyngstrom A1 Mohammed Milhem A1 Svetomir N Markovic A1 Tawnya Bowles A1 Omid Hamid A1 Leonel Hernandez-Aya A1 Joel Claveau A1 Sekwon Jang A1 Prejesh Philips A1 Shernan G Holtan A1 Montaser F Shaheen A1 Brendan Curti A1 William Schmidt A1 Marcus O Butler A1 Juan Paramo A1 Jose Lutzky A1 Arvinda Padmanabhan A1 Sajeve Thomas A1 Daniel Milton A1 Andrew Pecora A1 Takami Sato A1 Eddy Hsueh A1 Suprith Badarinath A1 John Keech A1 Sujith Kalmadi A1 Pallavi Kumar A1 Robert Weber A1 Edward Levine A1 Adam Berger A1 Anna Bar A1 J Thaddeus Beck A1 Jeffrey B Travers A1 Catalin Mihalcioiu A1 Brian Gastman A1 Peter Beitsch A1 Suthee Rapisuwon A1 John Glaspy A1 Edward C McCarron A1 Vinay Gupta A1 Deepti Behl A1 Brent Blumenstein A1 Joanna J Peterkin YR 2021 UL http://jitc.bmj.com/content/9/10/e003272.abstract AB 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.Data are available upon reasonable request.