Clinical Trials
Phase III Study

Phase III Study

MAVIS (Melanoma Antigen Vaccine Immunotherapy Study) is a multicenter, double-blind, placebo-controlled adaptive Phase III trial to assess the safety and efficacy of seviprotimut-L, with primary endpoints of recurrence-free survival (RFS) and overall survival (OS) in patients with melanoma at high risk of recurrence after definitive surgical resection. MAVIS is being conducted under a Special Protocol Assessment (SPA) agreement with the FDA.

Background

Seviprotimut-L is an allogeneic, polyvalent, partially purified shed melanoma antigens vaccine (alum adjuvanted) derived from three human melanoma cell lines. Prior formulations showed promising immunogenicity for T cell and antibody responses and improved survival in two small previous phase II clinical trials (see Phase II Studies). Part B1 of MAVIS was designed to assess the efficacy of seviprotimut-L in patients at high risk of recurrence after definitive surgical resection with a primary endpoint of recurrence-free survival (RFS).

Method

347 patients with AJCCv7 stage IIB-III cutaneous melanoma, after surgical resection, ages 18-75, ECOG PS 0-1, were enrolled and randomized 2:1 to seviprotimut-L 40 mcg or placebo, administered intradermally every 2 weeks x 5, then monthly x 4, then every 3 months to month 24. Patients were stratified by stage (IIB/C, IIIA, IIIB/C). The study was powered for assessment of RFS, with A target hazard ratio (HR) of 0.625, one-sided alpha of 0.10, and power 80%.

Results

By intent-to-treat (ITT) analysis, RFS was not significantly enhanced for seviprotimut-L in the overall study population but did trend slightly higher. However, strong responses were seen in two well-defined subpopulations based on disease stage and age at time of treatment. Specifically, interim efficacy analysis of subgroups based on pre-planned stratification suggested enhanced RFS for seviprotimut-L among two patient populations: those with AJCC Stage IIB/C melanoma and those under the age of 60.

Age has been identified as a cause of decreased immune competence1; thus, outcomes were assessed as a function of age as an effect modifier. Effects estimates for patients aged less than 60 years are favorable to seviprotimut-L in the overall population (Hazard Ratio= 0.61, 95% CI [0.36, 1.05]) and in the Stage IIB/IIC population (Hazard Ratio= 0.239, 95% CI [0.083, 0.69]).

Seviprotimut-L is well-tolerated with treatment-emergent adverse events (AEs) similar to placebo patients. There were no serious adverse events or Grade 4 or 5 adverse events in the 347 patients studied, and the vast majority of events were Grade 1-2 injection site reactions that were managed by topical cream/s or an over-the-counter antihistamine

Conclusions

Seviprotimut-L is very well tolerated. Subgroup efficacy analyses identified two populations who may benefit from Seviprotimut-L: those with AJCC stage IIB/C melanoma and those under the age of 60.

Dorshkind K, Swain S. Age-associated declines in immune system development and function: causes, consequences, and reversal. Curr Opin Immunol 2009; 21: 404-407

Recurrence-free Survival (RFS): Seviprotimut-L vs. Placebo

A. RFS for the Overall Patient Population

B. RFS for Stage IIB/C Patient Subgroup

C. RFS by Age for the Overall Patient Population

D. RFS by Age for Stage IIB/C Patients

____Table 1: Enrollment and adverse events	Seviprotimut-L	Placebo
N	230	117
AEs	96%	97%
Grade 3 AEs	12%	9%
Grade 4-5 AEs	0%	0%
Rx-related AEs	70%	73%
Rx-related SAEs	0%	0%
AEs leading to d/c study drug	0.9%	0.9%
Rx-related AEs leading to d/c study drug	0.4%	0%

Clinical TrialsPhase III Study

Phase III Study

Clinical Trials
Phase III Study