994P Efficacy and safety of capmatinib plus spartalizumab in treatment-naïve patients with advanced NSCLC harboring MET exon 14 skipping mutation

Abstract

Capmatinib (cap) is a selective MET inhibitor approved for patients (pts) with advanced NSCLC (aNSCLC) harboring MET exon 14 skipping mutation (METex14) showing ORR [95% CI] of 66.7% [53.3, 78.3] in treatment (tx)-naïve pts. Spartalizumab (sparta) is a monoclonal antibody targeting programmed death protein-1 (PD-1). Cap enhances T cell mediated antitumor response in mice treated with PD-1 inhibitors. Combining cap with sparta may be beneficial in aNSCLC pts with METex14. This phase II study consisted of 2 parts: open-label, single-arm run-in part, where pts received cap 400 mg orally BID + sparta 400 mg i.v Q4W followed by randomized, double-blind, placebo-controlled part to evaluate the efficacy and safety of cap+sparta vs cap+placebo. Tx-naïve aNSCLC pts with METex14 and without ALK or EGFR alterations were included. The primary endpoint was investigator-assessed ORR as per RECIST v1.1. Herein, we report data from the run-in part. At data cut-off (DCO) of Feb 01, 2022, 31 pts were included in the run-in part; median age: 73 (range: 52-89) years; females (51.6%) and ECOG PS of 0/1 in 38.7%/61.3% of pts. The ORR [95% CI] was 38.7% [21.8, 57.8] and DCR [95% CI] was 77.4% [58.9, 90.4]. Median DOR has not been reached. Median PFS [95% CI] is 13.3 months [9.3, NA] but data remains to mature further. The preliminary PK results of both drugs showed consistency with prior monotherapy studies. Most common Tx-related AEs (any grades [GR], ≥30%) were peripheral edema (71%), elevated serum creatinine (45.2%), elevated ALT and AST (35.5% each). No Tx-related GR 3/4 pneumonitis and no fatal toxicity has been reported. Higher rates of tx-related AEs leading to dose reduction/interruption (80.6%) and/or discontinuation (35.5%) were seen with cap+sparta regimen vs other cap monotherapy studies, suggesting poor tolerability to the combination. Thus, study enrollment was halted, and all ongoing pts were discontinued from sparta. At DCO, 15 pts remain on cap monotherapy. The addition of sparta to cap treatment was not well tolerated and resulted in modest antitumor activity when compared with data from other cap monotherapy studies in tx-naïve aNSCLC pts with METex14.