Avelumab (anti–PD-L1) in combination with crizotinib or lorlatinib in patients with previously treated advanced NSCLC: Phase 1b results from JAVELIN Lung 101.

Abstract

9008 Background: ALK tyrosine kinase inhibitors (TKIs) are standard of care for patients (pts) with advanced ALK+ NSCLC, and preclinical data suggest potential synergistic activity with checkpoint inhibitors in NSCLC irrespective of ALK status. Avelumab is a human anti–PD-L1 IgG1 monoclonal antibody approved in various countries for treatment of metastatic Merkel cell carcinoma, and in the US for advanced urothelial carcinoma that has progressed following platinum therapy. We report initial results from JAVELIN Lung 101 (NCT02584634), a phase 1b/2 dose-finding trial of avelumab + crizotinib (A+C) or the next-generation ALK TKI lorlatinib (A+L) in pts with advanced/metastatic ALK-negative/wildtype (ALK−) or ALK+ NSCLC, respectively. Methods: In phase 1b, pts with previously treated ALK− NSCLC received A (10 mg/kg Q2W) + C (250 mg BID) while pts with ALK+ NSCLC received A (10 mg/kg Q2W) + L (100 mg QD) (starting dose levels in each group). The primary endpoint was dose-limiting toxicities (DLTs); secondary endpoints included adverse events (AEs) and objective responses. Results: At data cutoff on Oct 27, 2017, 12 ALK− pts had received A+C and 28 ALK+ pts had received A+L. All ALK− pts had received prior anticancer therapy; ALK+ pts had received a median 2 prior ALK TKIs (range 1-3; data not reported for 1 ALK+ pt). DLTs occurred with A+C in 5 ALK− pts (41.7%): ALT and AST increase (2 pts each), febrile neutropenia, hepatitis, QT prolongation, and rash (1 pt each). No DLTs occurred with A+L in ALK+ pts. Grade ≥3 AEs of any causality occurred with A+C in 7 ALK− pts (58.3%; most common [≥10%] was ALT increase [16.7%, n = 2]), and with A+L in 15 ALK+ pts (53.6%; most common were hypertriglyceridemia [14.3%, n = 4] and GGT increase [10.7%, n = 3]). The confirmed objective response rate with A+C in ALK− pts was 16.7% (95% CI, 2.1-48.4; partial response [PR] in 2 pts), and with A+L in ALK+ pts was 46.4% (95% CI, 27.5-66.1; PR in 12 pts; complete response in 1 pt). Conclusions: A+L showed an acceptable safety profile, distinct from A+C, and promising antitumor activity in pts with ALK+ NSCLC, and will be evaluated in treatment-naive pts in phase 2. Clinical trial information: NCT02584634.