@article {Slingluffe003272, author = {Craig L Slingluff and Karl D Lewis and Robert Andtbacka and John Hyngstrom and Mohammed Milhem and Svetomir N Markovic and Tawnya Bowles and Omid Hamid and Leonel Hernandez-Aya and Joel Claveau and Sekwon Jang and Prejesh Philips and Shernan G Holtan and Montaser F Shaheen and Brendan Curti and William Schmidt and Marcus O Butler and Juan Paramo and Jose Lutzky and Arvinda Padmanabhan and Sajeve Thomas and Daniel Milton and Andrew Pecora and Takami Sato and Eddy Hsueh and Suprith Badarinath and John Keech and Sujith Kalmadi and Pallavi Kumar and Robert Weber and Edward Levine and Adam Berger and Anna Bar and J Thaddeus Beck and Jeffrey B Travers and Catalin Mihalcioiu and Brian Gastman and Peter Beitsch and Suthee Rapisuwon and John Glaspy and Edward C McCarron and Vinay Gupta and Deepti Behl and Brent Blumenstein and Joanna J Peterkin}, title = {Multicenter, double-blind, placebo-controlled trial of seviprotimut-L polyvalent melanoma vaccine in patients with post-resection melanoma at high risk of recurrence}, volume = {9}, number = {10}, elocation-id = {e003272}, year = {2021}, doi = {10.1136/jitc-2021-003272}, publisher = {BMJ Specialist Journals}, 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.Data are available upon reasonable request.}, URL = {https://jitc.bmj.com/content/9/10/e003272}, eprint = {https://jitc.bmj.com/content/9/10/e003272.full.pdf}, journal = {Journal for ImmunoTherapy of Cancer} }