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
Olivier Adotévi, Déwi Vernerey, P. Jacoulet, Aurélia Meurisse, Caroline Laheurte, Hamadi Almotlak, Marion Jacquin, Vincent Kaulek, Laura Boullerot, Marine Malfroy, Émeline Orillard, Guillaume Eberst, Aurélie Lagrange, Laure Favier, M. Gainet-Brun, Ludovic Doucet, Luís Teixeira, Zineb Ghrieb, Anne‐Laure Clairet, Yves Claude Guillaume, Marie Kroemer, Didier Hocquet, Mélanie Moltenis, Samuel Limat, Élisabeth Quoix, Céline Mascaux, D. Debieuvre, Christine Fagnoni-Legat, Christophe Borg, Virginie Westeel
Abstract
PURPOSE 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 AND METHODS 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. RESULTS 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 ( P = .015) and 4.5% (95% CI, 0.7 to 30.8) and 5.6 months (95% CI, 2.5 to 10) in nonresponders ( P = .005), respectively. CONCLUSION UCPVax was highly immunogenic and safe and provide interesting 1-year OS rate in heavily pretreated advanced NSCLC.