ARRY-382 in Combination with Pembrolizumab in Patients With Advanced Solid Tumors: Results From a Phase 1b/2 Study
Mené sur 19 patients atteints d'une tumeur solide de stade avancé, cet essai multicentrique de phase IB/II évalue la dose maximale tolérée de ARRY-382 (un inhibiteur sélectif du récepteur du facteur 1 de stimulation des colonies de granulocytes et de macrophages) en combinaison avec le pembrolizumab, et l'efficacité, du point de vue du taux de réponse objective, de cette combinaison
Purpose: ARRY-382 (PF-07265804) is a selective inhibitor of colony-stimulating factor-1 receptor. We evaluated the safety and preliminary efficacy of ARRY-382 plus pembrolizumab in patients with advanced solid tumors. Experimental Design: This was an open-label, multicenter, Phase 1b/2 study (NCT02880371) performed over September 1, 2016 to October 24, 2019. In the Phase 1b dose-escalation, patients with selected advanced solid tumors received ARRY-382 (starting dose 200 mg once daily [QD] orally) plus pembrolizumab (2 mg/kg intravenously [IV] every 3 weeks [Q3W]). Phase 2 patients had: pancreatic ductal adenocarcinoma (PDA); programmed cell death protein-1 (PD-1)/PD-ligand 1 (PD-L1) inhibitor-refractory (PD-1/PD-L1 IR) advanced solid tumors; or platinum-resistant ovarian cancer (prOVCA). Patients received ARRY-382 at the maximum tolerated dose (MTD) of 300 mg QD plus pembrolizumab 200 mg IV Q3W. Results: Primary endpoints of dose-limiting toxicities (Phase 1b) and objective response rate (Phase 2) were met. In Phase 1b, 19 patients received ARRY-382 200-400 mg. Three patients reported DLTs. The MTD of ARRY-382 (plus pembrolizumab) was 300 mg QD. In Phase 1b, 2 patients (10.5%) had confirmed PR: 1 with PDA and 1 with ovarian cancer, lasting 29.2 and 3.1 months, respectively. In Phase 2, there were 27, 19, and 11 patients in the PDA, PD-1/PD-L1 IR, and prOVCA cohorts, respectively. One patient (3.7%) with PDA had a partial response (PR) lasting 2.4 months. The most frequent ARRY-382-related adverse events were increased transaminases (10.5-83.3%) and increased creatine phosphokinase (18.2-50.0%). Conclusions: Although limited clinical benefit was observed, ARRY-382 plus pembrolizumab was well tolerated.