Department of Surgery, University of Virginia School of Medicine, Charlottesville, Virginia, USA
University of Colorado - Anschutz Medical Campus, Aurora, Colorado, USA.
J Immunother Cancer. 2021 Oct;9(10). doi: 10.1136/jitc-2021-003272.
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.
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.
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)).
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.
NCT01546571.
大多数晚期黑色素瘤患者在接受检查点阻断治疗后会复发。因此，需要能够安全地早期应用的免疫疗法，即在辅助治疗中应用。Seviprotimut-L 是一种含有人类黑色素瘤抗原的疫苗，加明矾。为了评估 seviprotimut-L 的疗效，启动了黑色素瘤抗原疫苗免疫治疗研究（MAVIS），这是一项三部分、双盲、安慰剂对照的 III 期临床试验。这里报告了第 B1 部分的结果。
手术后 AJCC V.7 分期为 IIB-III 期皮肤黑色素瘤的患者按 2:1 的比例随机分组，分层（IIB/C、IIIA、IIIB/C）接受 seviprotimut-L 40 mcg 或安慰剂。无复发生存期（RFS）是主要终点。假设 HR 为 0.625，单侧 alpha 为 0.10，功效 80%，目标入组 325 例患者。
对于随机分组的患者（n=347），两组之间平衡良好，seviprotimut-L 和安慰剂的治疗后不良事件相似。对于 RFS 的主要意向治疗终点，估计的 HR 为 0.881（95%CI：0.629 至 1.233），分层对数秩检验 p=0.46。然而，估计的 HR 并不均匀分布在随机分层的阶段，IIB/IIC、IIIA、IIIB/IIIC 阶段的 HR（95%CI）分别为 0.67（95%CI：0.37 至 1.19）、0.72（95%CI：0.35 至 1.50）和 1.19（95%CI：0.72 至 1.97）。在 IIB/IIC 分层中，RFS 的影响最大的是<60 岁的患者（HR=0.324（95%CI：0.121 至 0.864））和溃疡原发性黑色素瘤患者（HR=0.493（95%CI：0.255 至 0.952））。
seviprotimut-L 耐受性非常好。探索性疗效模型估计支持在 IIB/IIC 期患者中进一步研究，特别是年轻患者和溃疡黑色素瘤患者。
NCT01546571。
