Multicenter, double-blind, placebo-controlled trial of seviprotimut-L polyvalent melanoma vaccine in patients with post-resection melanoma at high risk of recurrence

• Published in: Journal for immunotherapy of cancer 2021-10, Vol.9 (10), p.e003272
• Main Authors: 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, Peterkin, Joanna J
• Format: Article
• Language: English
• Subjects: active; Adolescent; Adult; Aged; Aged, 80 and over; Aluminum; Antigens; Autoimmune diseases; Cancer; Cancer therapies; Cancer Vaccines - pharmacology; Cancer Vaccines - therapeutic use; Clinical trials; Clinical/Translational Cancer Immunotherapy; Double-Blind Method; Double-blind studies; Drug dosages; FDA approval; Female; Humans; Immunotherapy; Kinases; Lymphatic system; Male; Melanoma; Melanoma - drug therapy; Metastasis; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Proteins; Surgery; vaccination; Vaccines; Vaccines, Combined - pharmacology; Vaccines, Combined - therapeutic use; Young Adult
• ISSN: 2051-1426; 2051-1426
• DOI: 10.1136/jitc-2021-003272

BackgroundMost 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.MethodsPatients 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.ResultsFor 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