Jang, Sekwon

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.

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.

e14144 Background: There is little real-world evidence evaluating treatment patterns and outcomes with IO therapies for pts with advanced melanoma (aMEL). We present results from the OPTIMIzE (NCT02780089) study in pts with aMEL receiving IO therapies. Methods: OPTIMIzE is a US-based multisite (150 sites), community-based study of adult pts with aMEL. Pts receiving first-line (1L) nivolumab (NIVO)+ipilimumab (IPI), anti-PD-1 (NIVO/pembrolizumab), or IPI between 2011-2018 with a minimum 1 y of follow-up were included. Baseline characteristics, objective response rate (ORR), overall survival (OS), treatment-related adverse events (TRAEs), and quality of life (QoL) were analyzed. QoL assessments included the Functional Assessment of Cancer Therapy–Melanoma (FACT-M), EQ-5D index, and visual analog scale (VAS). Results: Cohort size: 81 NIVO+IPI, 147 anti-PD-1, and 16 IPI (IPI arm not included in the analysis). Overall, mean age was 64.5 y; 42% had BRAF mutation. Mean follow-up was 14.1 mo. Pts in the NIVO+IPI group were younger, had better ECOG performance status, and a higher likelihood of M1c disease and elevated LDH vs the anti-PD-1 group. ORR was higher for pts treated with NIVO+IPI vs anti-PD-1 (48% vs 33%, P= 0.08). Unadjusted 1-y OS was 78.4% for NIVO+IPI and 73.1% for anti-PD-1. In multivariate Cox model analysis, the hazard ratio for OS for NIVO+IPI vs anti-PD-1 was 0.78 (95% CI, 0.46–1.33; P= 0.36). Grade 3/4 TRAEs occurred in 53% and 22% of pts in the NIVO+IPI and anti-PD-1 groups, respectively ( P˂0.001). QoL changes from baseline were clinically meaningful for EQ-5D VAS and FACT-M in the NIVO+IPI group at 12 mo (Table). After adjusting for baseline covariates, the difference at 12 mo between NIVO+IPI vs anti-PD-1 was 6.7 ( P= 0.04) for EQ-5D VAS and 8.8 ( P= 0.02) for FACT-M. Conclusions: Safety and efficacy outcomes from this prospective real-world study are consistent with those reported in prior clinical trials in treatment-naive aMEL pts. No clinically meaningful deterioration in QoL measures was observed in either group. Clinical trial information: NCT02780089. [Table: see text]