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

Authors

• Craig L Slingluff, University of Virginia School of Medicine
• Karl D Lewis, University of Colorado
• Robert Andtbacka, Huntsman Cancer Institute Cancer Hospital
• John Hyngstrom
• Mohammed Milhem, The University of Iowa Hospitals and Clinics
• Svetomir N Markovic, Mayo Clinic Rochester
• Tawnya Bowles, Intermountain Medical Center
• Omid Hamid, Cedars-Sinai Medical Center Angeles Clinic and Research Institute
• Leonel Hernandez-Aya, Washington University School of Medicine in Saint Louis
• Joel Claveau, CHU de Quebec-Universite Laval
• Sekwon Jang, Inova Health System
• Prejesh Philips, University of Louisville
• Shernan G Holtan, University of Minnesota Academic Health Center
• Montaser F Shaheen, University of Arizona Medical Center
• Brendan Curti, Providence Portland Medical Center
• William Schmidt, Bend Memorial Clinic
• Marcus O Butler, Princess Margaret Hospital Cancer Centre
• Juan Paramo, Mount Sinai Medical Center
• Jose Lutzky, Sylvester Comprehensive Cancer Center
• Arvinda Padmanabhan, Baptist Health Lexington
• Sajeve Thomas, MD Anderson Cancer Center Orlando
• Daniel Milton, Investigative Clinical Research of Indiana
• Andrew Pecora, John Theurer Cancer Center
• Takami Sato, Thomas Jefferson UniversityFollow
• Eddy Hsueh, St. Louis University Hospital
• Suprith Badarinath, Cancer Specialists of North Florida
• John Keech, Multicare Institute for Research and Innovation
• Sujith Kalmadi, Ironwood Cancer and Research Centers
• Pallavi Kumar, Harry and Jeanette Weinberg Cancer Institute at Franklin Square
• Robert Weber, St. Mary's Hospital and Medical Center
• Edward Levine, Wake Forest School of Medicine
• Adam Berger, Rutgers Cancer Institute of New Jersey
• Anna Bar, Oregon Health & Science University
• J Thaddeus Beck, Highlands Oncology Group
• Jeffrey B Travers, Premier Health Partners Inc
• Catalin Mihalcioiu, Royal Victoria Hospital
• Brian Gastman, Cleveland Clinic
• Peter Beitsch, Cancer Solutions
• Suthee Rapisuwon, MedStar Washington Hospital Center
• John Glaspy, University of California Los Angeles
• Edward C McCarron, MedStar Franklin Square Medical Center
• Vinay Gupta, MedStar Franklin Square Medical Center
• Deepti Behl, Sutter Institute for Medical Research
• Brent Blumenstein, Trial Architecture Consulting
• Joanna J Peterkin, Polynoma

Document Type

Article

Publication Date

10-1-2021

Comments

This article is the author’s final published version in Journal for ImmunoTherapy of Cancer, Volume 9, Issue 10, October 2021, Article number e003272.

The published version is available at https://doi.org/10.1136/jitc-2021-003272. Copyright © Slingluff et al.

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.

Recommended Citation

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). Department of Medical Oncology Faculty Papers. Paper 157.
https://jdc.jefferson.edu/medoncfp/157

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

PubMed ID

34599031

Language

English