Department of Medical Oncology, University Hospital of Besançon, Besançon, France.
INSERM, EFS BFC, UMR1098, RIGHT, University of Bourgogne Franche-Comté, Besançon, France.
J Clin Oncol. 2023 Jan 10;41(2):373-384. doi: 10.1200/JCO.22.00096. Epub 2022 Sep 7.
Universal cancer peptide-based vaccine (UCPVax) is a therapeutic vaccine composed of two highly selected helper peptides to induce CD4+ T helper-1 response directed against telomerase. This phase Ib/IIa trial was designed to test the safety, immunogenicity, and efficacy of a three-dose schedule in patients with metastatic non-small-cell lung cancer (NSCLC).
Patients with refractory NSCLC were assigned to receive three vaccination doses of UCPVax (0.25 mg, 0.5 mg, and 1 mg) using a Bayesian-based phase Ib followed by phase IIa de-escalating design. The primary end points were dose-limiting toxicity and immune response after three first doses of vaccine. Secondary end points were overall survival (OS) and progression-free survival at 1 year.
A total of 59 patients received UCPVax; 95% had three prior lines of systemic therapy. No dose-limiting toxicity was observed in 15 patients treated in phase Ib. The maximum tolerated dose was 1 mg. Fifty-one patients were eligible for phase IIa. The third and sixth dose of UCPVax induced specific CD4+ T helper 1 response in 56% and 87.2% of patients, respectively, with no difference between three dose levels. Twenty-one (39%) patients achieved disease control (stable disease, n = 20; complete response, n = 1). The 1-year OS was 34.1% (95% CI, 23.1 to 50.4), and the median OS was 9.7 months, with no significant difference between dose levels. The 1-year progression-free survival and the median OS were 17.2% (95% CI, 7.8 to 38.3) and 11.6 months (95% CI, 9.7 to 16.7) in immune responders ( = .015) and 4.5% (95% CI, 0.7 to 30.8) and 5.6 months (95% CI, 2.5 to 10) in nonresponders ( = .005), respectively.
UCPVax was highly immunogenic and safe and provide interesting 1-year OS rate in heavily pretreated advanced NSCLC.
通用癌症肽疫苗（UCPVax）是一种由两种高度选择的辅助肽组成的治疗性疫苗，可诱导针对端粒酶的 CD4+T 辅助 1 反应。这项 Ib/IIa 期试验旨在测试三剂方案在转移性非小细胞肺癌（NSCLC）患者中的安全性、免疫原性和疗效。
将难治性 NSCLC 患者分配接受三剂 UCPVax（0.25mg、0.5mg 和 1mg）疫苗接种，采用基于贝叶斯的 Ib 期试验，随后进行 IIa 期逐步降低剂量设计。主要终点是前 3 剂疫苗接种后的剂量限制性毒性和免疫反应。次要终点是总生存期（OS）和 1 年时的无进展生存期。
共 59 例患者接受了 UCPVax 治疗；95%的患者有 3 种以上的系统治疗。在 15 例接受 Ib 期治疗的患者中未观察到剂量限制性毒性。最大耐受剂量为 1mg。51 例患者符合 IIa 期标准。第 3 剂和第 6 剂 UCPVax 分别诱导 56%和 87.2%的患者产生特异性 CD4+T 辅助 1 反应，3 个剂量水平之间无差异。21 例（39%）患者达到疾病控制（稳定疾病，n=20；完全缓解，n=1）。1 年 OS 为 34.1%（95%CI，23.1 至 50.4），中位 OS 为 9.7 个月，剂量水平之间无显著差异。免疫应答者的 1 年无进展生存期和中位 OS 分别为 17.2%（95%CI，7.8 至 38.3）和 11.6 个月（95%CI，9.7 至 16.7），而无应答者分别为 4.5%（95%CI，0.7 至 30.8）和 5.6 个月（95%CI，2.5 至 10）（=0.015）。
UCPVax 具有高度的免疫原性和安全性，并为晚期 NSCLC 患者提供了有趣的 1 年 OS 率。
