背景:免疫治疗难治性黑色素瘤的治疗选择尚未满足。MASTERKEY-115第二阶段,开放标签,多中心试验评估了talimogenelaherparepvec(T-VEC)加pembrolizumab在晚期黑色素瘤中的作用,该黑色素瘤在先前的程序性细胞死亡蛋白-1(PD-1)抑制剂上进展。
方法:队列1和2包括原发或获得性耐药的患者(不可切除/转移性黑色素瘤),分别,以及最后一次抗PD-1剂量后12周内的疾病进展。队列3和4包括接受完整手术的患者(可切除疾病),接受抗PD-1辅助治疗,并出现复发。队列3在开始辅助抗PD-1治疗后且在确诊复发前<6个月无病,队列4在≥6个月。主要终点是根据RECISTv1.1的客观缓解率(ORR)。次要终点包括完全反应率(CRR),根据RECISTv1.1和irRC-RECIST,疾病控制率(DCR)和无进展生存期(PFS),和安全。
结果:在72名患者中,71人接受了治疗。ORR(95%CI)为0%,6.7%(0.2-32.0),40.0%(16.3-67.7),队列1-4中分别为46.7%(21.3-73.4);iORR为3.8%(0.1-19.6),6.7%(0.2-32.0),53.3%(26.6-78.7),和46.7%(21.3-73.4)。iCRR为0%,0%,13.3%,和13.3%。iPFS中位数(月)为5.5,8.2,不可估计[NE],队列1-4分别为NE;iDCR为50.0%,40.0%,73.3%,和86.7%。治疗相关不良事件(TRAEs),≥3级TRAEs,严重的AE,54例(76.1%)发生致命不良事件,9(12.7%),24(33.8%),和10名(14.1%)患者,分别。
结论:T-VEC-pembrolizumab在PD-1难治性黑色素瘤中表现出抗肿瘤活性和耐受性,特别是在抗PD-1辅助治疗后疾病复发的患者。
背景:ClinicalTrials.gov标识符-NCT04068181。
BACKGROUND: Treatment options for immunotherapy-refractory melanoma are an unmet need. The MASTERKEY-115 phase II, open-label, multicenter
trial evaluated talimogene laherparepvec (T-VEC) plus pembrolizumab in advanced melanoma that progressed on prior programmed cell death protein-1 (PD-1) inhibitors.
METHODS: Cohorts 1 and 2 comprised patients (unresectable/metastatic melanoma) who had primary or acquired resistance, respectively, and disease progression within 12 weeks of their last anti-PD-1 dose. Cohorts 3 and 4 comprised patients (resectable disease) who underwent complete surgery, received adjuvant anti-PD-1, and experienced recurrence. Cohort 3 were disease-free for < 6 months and cohort 4 for ≥ 6 months after starting the adjuvant anti-PD-1 therapy and before confirmed recurrence. The primary endpoint was objective response rate (ORR) per RECIST v1.1. Secondary endpoints included complete response rate (CRR), disease control rate (DCR) and progression-free survival (PFS) per RECIST v1.1 and irRC-RECIST, and safety.
RESULTS: Of the 72 enrolled patients, 71 were treated. The ORR (95% CI) was 0%, 6.7% (0.2-32.0), 40.0% (16.3-67.7), and 46.7% (21.3-73.4) in cohorts 1-4, respectively; iORR was 3.8% (0.1-19.6), 6.7% (0.2-32.0), 53.3% (26.6-78.7), and 46.7% (21.3-73.4). iCRR was 0%, 0%, 13.3%, and 13.3%. Median iPFS (months) was 5.5, 8.2, not estimable [NE], and NE for cohorts 1-4, respectively; iDCR was 50.0%, 40.0%, 73.3%, and 86.7%. Treatment-related adverse events (TRAEs), grade ≥ 3 TRAEs, serious AEs, and fatal AEs occurred in 54 (76.1%), 9 (12.7%), 24 (33.8%), and 10 (14.1%) patients, respectively.
CONCLUSIONS: T-VEC-pembrolizumab demonstrated antitumor activity and tolerability in PD-1-refractory melanoma, specifically in patients with disease recurrence on or after adjuvant anti-PD-1.
BACKGROUND: ClinicalTrials.gov identifier - NCT04068181.