Open-Label, Phase 1 Study of Nivolumab Combined With nab-Paclitaxel Plus Gemcitabine in Advanced Pancreatic Cancer
Mené sur 50 patients atteints d’un cancer du pancréas de stade localement avancé ou métastatique, cet essai de phase I évalue la dose maximale tolérée et l’efficacité, du point de vue de la survie sans progression, de la survie globale et du taux de réponse, du nivolumab en combinaison avec le nab-paclitaxel et la gemcitabine
Résumé en anglais
Purpose: Assess safety and efficacy of nivolumab plus nab-paclitaxel and gemcitabine in patients with locally advanced/metastatic pancreatic cancer in a 2-part, open-label, phase 1 trial. Experimental Design: Fifty chemotherapy-naive patients received nab-paclitaxel 125 mg/m2 plus gemcitabine 1000 mg/m2 (days 1, 8, and 15) and nivolumab 3 mg/kg (days 1 and 15) in 28-day cycles. The primary endpoints were dose-limiting toxicities (DLTs; part 1) and grade 3/4 treatment-emergent adverse events (TEAEs) or treatment discontinuation due to TEAEs (parts 1/2). Secondary efficacy endpoints were progression-free survival (PFS), overall survival (OS), and response. Assessment of programmed cell death-ligand 1 (PD-L1) expression was an exploratory endpoint; additional biomarkers were assessed post hoc. Results: One DLT (hepatitis) was reported in part 1 among 6 DLT-evaluable patients; 48/50 patients experienced grade 3/4 TEAEs and 18 discontinued treatment due to TEAEs. One grade 5 TEAE (respiratory failure) was reported. Median (95% CI) PFS/OS was 5.5 (3.25-7.20 months)/9.9 (6.74-12.16 months) months, respectively (median follow-up for OS, 13.6 months [95% CI, 12.06-23.49 months]). Overall response rate (95% CI) was 18% (8.6%-31.4%). Median PFS/OS was 5.5/9.7 months (PD-L1 <5%) and 6.8/11.6 months (PD-L1 ?5%), respectively. Proportion of peripheral Ki67+ CD8+/CD4+ cells increased significantly from baseline to cycle 3; median peak on-treatment Ki67+ CD8+ T-cell values were higher in responders than in nonresponders. Conclusions: The safety profile of nivolumab plus nab-paclitaxel and gemcitabine at standard doses in advanced pancreatic cancer was manageable, with no unexpected safety signals. Overall, the clinical results of this study do not support further investigation.
