通用型癌症肽基疫苗对难治性晚期非小细胞肺癌患者的安全性、免疫原性和1年疗效:一项Ib期/ IIa期研究

SCI

27 September 2022

Safety, Immunogenicity, and 1-Year Efficacy of Universal Cancer Peptide–Based Vaccine in Patients With Refractory Advanced Non–Small-Cell Lung Cancer: A Phase Ib/Phase IIa De-Escalation Study

( J Clin Oncol;IF:50.717 )

Adotévi O, Vernerey D, Jacoulet P et al. Safety, Immunogenicity, and 1-Year Efficacy of Universal Cancer Peptide-Based Vaccine in Patients With Refractory Advanced Non-Small-Cell Lung Cancer: A Phase Ib/Phase IIa De-Escalation Study. J Clin Oncol 2022; Jco2200096. DOI: 10.1200/jco.22.00096

CORRESPONDING AUTHOR：Olivier Adot´ evi, MD, PhD, Department of Medical Oncology, University Hospital of Besançon, 25000 Besançon, France; e-mail: olivier.adotevi@univ-fcomte.fr.

PURPOSE 目的

Universal cancer peptide–based vaccine (UCPVax) is a therapeutic vaccine composed of two highly selected helper peptides to induce CD41 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).

通用癌症肽基疫苗(UCPVax)是一种治疗性疫苗，由两种高度选择的辅助肽组成，诱导CD4+ T辅助-1靶向端粒酶反应。这项Ib/IIa期试验旨在测试三剂量方案在转移性非小细胞肺癌(NSCLC)患者中的安全性、免疫原性和有效性。

PATIENTS AND METHODS 患者和方法

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.

难治性NSCLC患者被分配接受三剂UCPVax疫苗接种(0.25 mg, 0.5 mg，和1 mg)，采用基于贝叶斯的Ib期和IIa期降级设计。主要终点是首次接种三剂疫苗后的剂量限制毒性和免疫反应。次要终点为总生存期(OS)和1年无进展生存期。

RESULTS 结果

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 CD41 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, n520; complete response, n51). 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 (P=5 .015) and 4.5% (95% CI, 0.7 to 30.8) and 5.6 months (95% CI, 2.5 to 10) in nonresponders (P=5 .005), respectively. 

共有59例患者接受了UCPVax治疗;95%的患者既往有三线全身治疗。在Ib期治疗的15例患者中未观察到剂量限制毒性。最大耐受剂量为1 mg。51名患者符合IIa期的条件。第三和第六剂UCPVax分别在56%和87.2%的患者中诱导了特异性CD41 T辅助1反应，三个剂量水平之间没有差异。21例(39%)患者实现了疾病控制(病情稳定，n=20;完整的反应,n=1)。1年的OS为34.1% (95% CI ：23.1 ~ 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 ~ 38.3)和11.6个月(95% CI, 9.7 ~ 16.7)，无应答者的1年无进展生存期和中位OS分别为4.5% (95% CI, 0.7 ~ 30.8)和5.6个月(95% CI, 2.5 ~ 10，P= .005)。

CONCLUSION 结论

UCPVax was highly immunogenic and safe and provide interesting 1-year OS rate in heavily pretreated advanced NSCLC.

UCPVax具有高免疫原性和安全性，在许多预处理的晚期NSCLC中提供了有趣的1年OS率。

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