Abstract
Final analysis of relapse-free survival in a multicenter, double-blind, placebo-controlled trial of seviprotimut-L polyvalent melanoma vaccine after resection of high-risk melanoma
Journal of clinical oncology, Vol.38(15_suppl), pp.10017-10017
05/20/2020
DOI: 10.1200/JCO.2020.38.15_suppl.10017
Abstract
10017
Background: Seviprotimut-L is a vaccine prepared from antigens of 3 human melanoma cell lines, administered with alum. Prior formulations induced T cell and antibody responses and improved survival in a small phase II clinical trial. Part B1 of MAVIS (Melanoma Antigen Vaccine Immunotherapy Study, a three part, Phase III clinical program), was a multicenter, double-blind, placebo-controlled trial to assess efficacy of seviprotimut-L, with the primary endpoint of relapse-free survival (RFS). The goal of Part B1 was to guide design of the pivotal Part B2. Methods: Patients with AJCC v7 stage IIB-III cutaneous melanoma, after surgical resection, age 18-75, ECOG PS 0-1, were randomized 2:1 to seviprotimut-L 40 mcg or placebo, injected subcutaneously every 2 weeks x 5, then monthly x 4, then every 3 months x 9. Patients were stratified by stage (IIB/C, IIIA, IIIB/C). Target enrollment was 325. The study was powered for assessment of RFS, with target hazard ratio (HR) of 0.625, one-sided alpha of 0.10, and power 80%. Final data are presented. Results: 347 patients were randomized. Arms were well-balanced. Treatment-related adverse events (AEs) led to discontinuation in 0.4% and 0%, respectively, for vaccine and placebo arms. There were no treatment-related SAEs. By intent-to-treat (ITT) analysis, RFS was not significantly longer for seviprotimut-L in the full study population but trended toward benefit (HR 0.88). Subgroup analysis based on planned stratification revealed the hazard ratio (HR) for the Stage IIB/IIC subset (randomization stratum, n=111) to be 0.65 (95% CI [0.37, 1.17]), favoring seviprotimut-L. Age can decrease immune competence: RFS was longer with vaccine for patients age <60 overall (N = 191, HR = 0.64 [0.38, 1.08]) and among Stage IIB/C patients (N = 52, HR = 0.32 [0.12, 0.86]). The effect modification interaction p value for age for stage IIB/IIC patients was 0.056. In a multivariable RFS model, for IIB/IIC patients <60 with ulceration (n=38), HR = 0.209 [0.07,0.61]. For overall survival, for patients < 60, HR = 0.41 [0.33,1.14] (n=191, 19 deaths) and for those ≥60, HR = 0.92 [0.39,2.12] (n = 156, 24 deaths). Conclusions: Seviprotimut-L is very well-tolerated. Subgroup efficacy analyses identified populations who may benefit from Seviprotimut-L: those with Stage IIB/IIC melanoma and those under age 60. These data support design of the definitive part B2 of the MAVIS phase III trial to test seviprotimut-L for stage IIB/C patients, with stratification by age and ulceration. Clinical trial information: NCT01546571.
Details
- Title: Subtitle
- Final analysis of relapse-free survival in a multicenter, double-blind, placebo-controlled trial of seviprotimut-L polyvalent melanoma vaccine after resection of high-risk melanoma
- Creators
- Craig L. Slingluff - University of VirginiaBrent A. Blumenstein - Trial Architecture Consulting, Washington, DCKarl D. Lewis - University of Colorado DenverRobert Hans Ingemar Andtbacka - University of UtahJohn Robert Hyngstrom - University of UtahMohammed M. Milhem - University of IowaSvetomir Markovic - Mayo ClinicOmid Hamid - Angeles Clinic and Research InstituteLeonel Fernando Hernandez-Aya - University of Michigain Health System, Ann Arbor, MITawnya Lynn Bowles - Intermountain HealthcarePrejesh Philips - University of LouisvilleSekwon Jang - Inova Health SystemJose Lutzky - Mount Sinai Medical CenterAnna Bar - OHSU Knight Cancer Institute, Portland, ORPeter D. Beitsch - Dallas Surgical Group
- Resource Type
- Abstract
- Publication Details
- Journal of clinical oncology, Vol.38(15_suppl), pp.10017-10017
- DOI
- 10.1200/JCO.2020.38.15_suppl.10017
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Grant note
- name: Polynoma
- Language
- English
- Date published
- 05/20/2020
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984363292202771
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