Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
Faculty of Medicine, University of Oslo, Oslo, Norway.
Clin Cancer Res. 2023 Aug 15;29(16):3026-3036. doi: 10.1158/1078-0432.CCR-23-0416.
Cancer vaccines represent a novel treatment modality with a complementary mode of action addressing a crucial bottleneck for checkpoint inhibitor (CPI) efficacy. CPIs are expected to release brakes in T-cell responses elicited by vaccination, leading to more robust immune responses. Increased antitumor T-cell responses may confer increased antitumor activity in patients with less immunogenic tumors, a subgroup expected to achieve reduced benefit from CPIs alone. In this trial, a telomerase-based vaccine was combined with pembrolizumab to assess the safety and clinical activity in patients with melanoma.
Thirty treatment-naïve patients with advanced melanoma were enrolled. Patients received intradermal injections of UV1 with adjuvant GM-CSF at two dose levels, and pembrolizumab according to the label. Blood samples were assessed for vaccine-induced T-cell responses, and tumor tissues were collected for translational analyses. The primary endpoint was safety, with secondary objectives including progression-free survival (PFS), overall survival (OS), and objective response rate (ORR).
The combination was considered safe and well-tolerated. Grade 3 adverse events were observed in 20% of patients, with no grade 4 or 5 adverse events reported. Vaccination-related adverse events were mostly mild injection site reactions. The median PFS was 18.9 months, and the 1- and 2-year OS rates were 86.7% and 73.3%, respectively. The ORR was 56.7%, with 33.3% achieving complete responses. Vaccine-induced immune responses were observed in evaluable patients, and inflammatory changes were detected in posttreatment biopsies.
Encouraging safety and preliminary efficacy were observed. Randomized phase II trials are currently ongoing.
癌症疫苗代表了一种新的治疗方式，具有互补的作用模式，可解决检查点抑制剂（CPI）疗效的关键瓶颈。CPI 有望释放疫苗引发的 T 细胞反应的制动，从而产生更强大的免疫反应。增加抗肿瘤 T 细胞反应可能会赋予对免疫原性较低的肿瘤患者更高的抗肿瘤活性，预计这一亚组仅从 CPI 中获益有限。在这项试验中，一种基于端粒酶的疫苗与 pembrolizumab 联合使用，以评估其在黑色素瘤患者中的安全性和临床活性。
招募了 30 名初治的晚期黑色素瘤患者。患者接受了两种剂量水平的 UV1 皮内注射，并联合使用 GM-CSF 作为佐剂，以及根据标签规定使用 pembrolizumab。评估了疫苗诱导的 T 细胞反应的血液样本，并收集了肿瘤组织进行转化分析。主要终点是安全性，次要目标包括无进展生存期（PFS）、总生存期（OS）和客观缓解率（ORR）。
联合治疗被认为是安全且耐受良好的。20%的患者出现 3 级不良事件，无 4 级或 5 级不良事件报告。与疫苗相关的不良事件主要是轻微的注射部位反应。中位 PFS 为 18.9 个月，1 年和 2 年 OS 率分别为 86.7%和 73.3%。ORR 为 56.7%，其中 33.3%达到完全缓解。在可评估的患者中观察到了疫苗诱导的免疫反应，并在治疗后活检中检测到了炎症变化。
观察到令人鼓舞的安全性和初步疗效。目前正在进行随机 II 期试验。
