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.
| Original language | English (US) |
|---|---|
| Article number | e003272 |
| Journal | Journal for ImmunoTherapy of Cancer |
| Volume | 9 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 1 2021 |
Bibliographical note
Funding Information:1Department of Surgery, University of Virginia School of Medicine, Charlottesville, Virginia, USA 2University of Colorado - Anschutz Medical Campus, Aurora, Colorado, USA 3Huntsman Cancer Institute Cancer Hospital, Salt Lake City, Utah, USA 4The University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA 5Mayo Clinic Rochester, Rochester, Minnesota, USA 6Intermountain Medical Center, Murray, Utah, USA 7Cedars-Sinai Medical Center Angeles Clinic and Research Institute, Santa Monica, California, USA 8Department of Medicine, Washington University School of Medicine in Saint Louis, Saint Louis, Missouri, USA 9CHU de Quebec-Universite Laval, Quebec, Québec, Canada 10Department of Medical Oncology, Inova Health System, Falls Church, Virginia, USA 11University of Louisville, Louisville, Kentucky, USA 12University of Minnesota Academic Health Center, Minneapolis, Minnesota, USA 13University of Arizona Medical Center - University Campus, Tucson, Arizona, USA 14Earle A Chiles Research Institute, Providence Portland Medical Center, Portland, Oregon, USA 15Bend Memorial Clinic, Bend, Oregon, USA 16Princess Margaret Hospital Cancer Centre, Toronto, Ontario, Canada 17Mount Sinai Medical Center, Miami Beach, Florida, USA 18Department of Oncology, Sylvester Comprehensive Cancer Center, Miami, Florida, USA 19Baptist Health Lexington, Lexington, Kentucky, USA 20MD Anderson Cancer Center Orlando, Orlando, Florida, USA 21Investigative Clinical Research of Indiana, Indianapolis, Indiana, USA 22Department of Oncology, John Theurer Cancer Center, Hackensack, New Jersey, USA 23Department of Medical Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA 24St. Louis University Hospital, St. Louis, Missouri, USA 25Cancer Specialists of North Florida, Jacksonville, Florida, USA 26Multicare Institute for Research and Innovation, Tacoma, Washington, USA 27Ironwood Cancer and Research Centers, Chandler, Arizona, USA 28Harry and Jeanette Weinberg Cancer Institute at Franklin Square, Baltimore, Maryland, USA 29St. Mary's Hospital and Medical Center, San Francisco, California, USA 30Wake Forest School of Medicine, Winston-Salem, North Carolina, USA 31Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA 32Oregon Health & Science University, Portland, Oregon, USA 33Department of Medical Oncology, Highlands Oncology Group, Fayetteville, Arkansas, USA 34Premier Health Partners Inc, Dayton, Ohio, USA 35Royal Victoria Hospital, Montreal, Québec, Canada 36Department of Plastic Surgery, Cleveland Clinic, Cleveland, Ohio, USA 37Cancer Solutions, Dallas, Texas, USA 38Department of Oncology, Georgetown University Medical Center, Washington, District of Columbia, USA 39Department of Hematology/Oncology, MedStar Washington Hospital Center, Washington, District of Columbia, USA 40University of California Los Angeles, Los Angeles, California, USA 41MedStar Franklin Square Medical Center, Baltimore, Maryland, USA 42Sutter Institute for Medical Research, Sacramento, California, USA 43Trial Architecture Consulting, Chevy Chase, Maryland, USA 44Polynoma, San Diego, California, USA Acknowledgements We acknowledge participation of all the patients and their families, support of all investigators and clinical coordinators responsible for enrolling patients to this trial, Jean-Claude Bystryn for his initial work on this vaccine strategy, and funding support from Polynoma. We also acknowledge the support of the Maryland Melanoma Center (Amy Avergas, MSIT, MBA; Ed McCarron, MD; Vinay Gupta, MD); Kathleen Haden, NP, at the University of Virginia Cancer Center.
Publisher Copyright:
© Author(s) (or their employer(s)) 2021.
Keywords
- active
- immunotherapy
- melanoma
- vaccination
