TY - JOUR 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 DO - 10.1136/jitc-2021-003272 VL - 9 IS - 10 SP - e003272 AU - Craig L Slingluff AU - Karl D Lewis AU - Robert Andtbacka AU - John Hyngstrom AU - Mohammed Milhem AU - Svetomir N Markovic AU - Tawnya Bowles AU - Omid Hamid AU - Leonel Hernandez-Aya AU - Joel Claveau AU - Sekwon Jang AU - Prejesh Philips AU - Shernan G Holtan AU - Montaser F Shaheen AU - Brendan Curti AU - William Schmidt AU - Marcus O Butler AU - Juan Paramo AU - Jose Lutzky AU - Arvinda Padmanabhan AU - Sajeve Thomas AU - Daniel Milton AU - Andrew Pecora AU - Takami Sato AU - Eddy Hsueh AU - Suprith Badarinath AU - John Keech AU - Sujith Kalmadi AU - Pallavi Kumar AU - Robert Weber AU - Edward Levine AU - Adam Berger AU - Anna Bar AU - J Thaddeus Beck AU - Jeffrey B Travers AU - Catalin Mihalcioiu AU - Brian Gastman AU - Peter Beitsch AU - Suthee Rapisuwon AU - John Glaspy AU - Edward C McCarron AU - Vinay Gupta AU - Deepti Behl AU - Brent Blumenstein AU - Joanna J Peterkin Y1 - 2021/10/01 UR - http://jitc.bmj.com/content/9/10/e003272.abstract N2 - 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. ER -