Multicenter, double-blind, placebo-controlled trial of seviprotimut-L polyvalent melanoma vaccine in patients with post-resection melanoma at high risk of recurrence.
J Immunother Cancer
oregon; portland; chiles
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(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.
Earle A. Chiles Research Institute
Slingluff, Craig L; Lewis, Karl D; Andtbacka, Robert; Hyngstrom, John; Milhem, Mohammed; Markovic, Svetomir N; Bowles, Tawnya; Hamid, Omid; Hernandez-Aya, Leonel; Claveau, Joel; Jang, Sekwon; Philips, Prejesh; Holtan, Shernan G; Shaheen, Montaser F; Curti, Brendan; Schmidt, William; Butler, Marcus O; Paramo, Juan; Lutzky, Jose; Padmanabhan, Arvinda; Thomas, Sajeve; Milton, Daniel; Pecora, Andrew; Sato, Takami; Hsueh, Eddy; Badarinath, Suprith; Keech, John; Kalmadi, Sujith; Kumar, Pallavi; Weber, Robert; Levine, Edward; Berger, Adam; Bar, Anna; Beck, J Thaddeus; Travers, Jeffrey B; Mihalcioiu, Catalin; Gastman, Brian; Beitsch, Peter; Rapisuwon, Suthee; Glaspy, John; McCarron, Edward C; Gupta, Vinay; Behl, Deepti; Blumenstein, Brent; and Peterkin, Joanna J, "Multicenter, double-blind, placebo-controlled trial of seviprotimut-L polyvalent melanoma vaccine in patients with post-resection melanoma at high risk of recurrence." (2021). Articles, Abstracts, and Reports. 5350.