Journal for ImmunoTherapy of Cancer (Oct 2021)
Multicenter, double-blind, placebo-controlled trial of seviprotimut-L polyvalent melanoma vaccine in patients with post-resection melanoma at high risk of recurrence
- Omid Hamid,
- Brendan Curti,
- Craig L Slingluff,
- Mohammed Milhem,
- Jose Lutzky,
- Suthee Rapisuwon,
- Brian Gastman,
- Takami Sato,
- Marcus O Butler,
- Robert Andtbacka,
- Eddy Hsueh,
- Robert Weber,
- John Glaspy,
- Sekwon Jang,
- Sajeve Thomas,
- Karl D Lewis,
- Leonel Hernandez-Aya,
- John Hyngstrom,
- Adam Berger,
- Edward Levine,
- Montaser F Shaheen,
- Vinay Gupta,
- Svetomir N Markovic,
- Tawnya Bowles,
- Joel Claveau,
- Prejesh Philips,
- Shernan G Holtan,
- William Schmidt,
- Juan Paramo,
- Arvinda Padmanabhan,
- Daniel Milton,
- Andrew Pecora,
- Suprith Badarinath,
- John Keech,
- Sujith Kalmadi,
- Pallavi Kumar,
- Anna Bar,
- J Thaddeus Beck,
- Jeffrey B Travers,
- Catalin Mihalcioiu,
- Peter Beitsch,
- Edward C McCarron,
- Deepti Behl,
- Brent Blumenstein,
- Joanna J Peterkin
Affiliations
- Omid Hamid
- 4The Angeles Clinic and Research Institute, a Cedars Sinai Affiliate, Los Angeles, CA, USA
- Brendan Curti
- Earle A Chiles Research Institute, Providence Portland Medical Center, Portland, Oregon, USA
- Craig L Slingluff
- Department of Surgery, University of Virginia School of Medicine, Charlottesville, Virginia, USA
- Mohammed Milhem
- University of Iowa Hospitals and Clinics, Iowa City, IA, USA
- Jose Lutzky
- 3University of Miami Sylvester Comprehensive Cancer Center, Miami, FL, USA
- Suthee Rapisuwon
- Department of Hematology/Oncology, MedStar Washington Hospital Center, Washington, District of Columbia, USA
- Brian Gastman
- 4Department of Plastic and Reconstructive Surgery, Cleveland Clinic, Cleveland, OH, USA
- Takami Sato
- Department of Medical Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
- Marcus O Butler
- 2University Health Network, Toronto, ON, Canada
- Robert Andtbacka
- Huntsman Cancer Institute Cancer Hospital, Salt Lake City, Utah, USA
- Eddy Hsueh
- St. Louis University Hospital, St. Louis, Missouri, USA
- Robert Weber
- St. Mary`s Hospital and Medical Center, San Francisco, California, USA
- John Glaspy
- University of California Los Angeles, Los Angeles, California, USA
- Sekwon Jang
- Department of Medical Oncology, Inova Health System, Falls Church, Virginia, USA
- Sajeve Thomas
- 14Orlando Health Cancer Institute, Orlando, FL, USA
- Karl D Lewis
- University of Colorado School of Medicine, Aurora, Colorado, USA
- Leonel Hernandez-Aya
- Department of Medicine, Washington University School of Medicine in Saint Louis, Saint Louis, Missouri, USA
- John Hyngstrom
- 11University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA
- Adam Berger
- Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA
- Edward Levine
- Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
- Montaser F Shaheen
- University of Arizona Medical Center - University Campus, Tucson, Arizona, USA
- Vinay Gupta
- MedStar Franklin Square Medical Center, Baltimore, Maryland, USA
- Svetomir N Markovic
- Mayo Clinic Rochester, Rochester, Minnesota, USA
- Tawnya Bowles
- Intermountain Medical Center, Murray, Utah, USA
- Joel Claveau
- CHU de Quebec-Universite Laval, Quebec, Québec, Canada
- Prejesh Philips
- University of Louisville, Louisville, Kentucky, USA
- Shernan G Holtan
- University of Minnesota Academic Health Center, Minneapolis, Minnesota, USA
- William Schmidt
- Bend Memorial Clinic, Bend, Oregon, USA
- Juan Paramo
- Mount Sinai Medical Center, Miami Beach, Florida, USA
- Arvinda Padmanabhan
- Baptist Health Lexington, Lexington, Kentucky, USA
- Daniel Milton
- Investigative Clinical Research of Indiana, Indianapolis, Indiana, USA
- Andrew Pecora
- Department of Oncology, John Theurer Cancer Center, Hackensack, New Jersey, USA
- Suprith Badarinath
- Cancer Specialists of North Florida, Jacksonville, Florida, USA
- John Keech
- Multicare Institute for Research and Innovation, Tacoma, Washington, USA
- Sujith Kalmadi
- Ironwood Cancer and Research Centers, Chandler, Arizona, USA
- Pallavi Kumar
- Harry and Jeanette Weinberg Cancer Institute at Franklin Square, Baltimore, Maryland, USA
- Anna Bar
- Oregon Health & Science University, Portland, Oregon, USA
- J Thaddeus Beck
- Department of Medical Oncology, Highlands Oncology Group, Fayetteville, Arkansas, USA
- Jeffrey B Travers
- Premier Health Partners Inc, Dayton, Ohio, USA
- Catalin Mihalcioiu
- Royal Victoria Hospital, Montreal, Québec, Canada
- Peter Beitsch
- Cancer Solutions, Dallas, Texas, USA
- Edward C McCarron
- MedStar Franklin Square Medical Center, Baltimore, Maryland, USA
- Deepti Behl
- Sutter Institute for Medical Research, Sacramento, California, USA
- Brent Blumenstein
- Trial Architecture Consulting, Chevy Chase, Maryland, USA
- Joanna J Peterkin
- Polynoma, San Diego, California, USA
- DOI
- https://doi.org/10.1136/jitc-2021-003272
- Journal volume & issue
-
Vol. 9,
no. 10
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.
