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 swish supreme glide track white 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 here 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.