Safety and clinical activity of MK-3475 as initial therapy in patients with advanced non-small cell lung cancer (NSCLC).

8007 Background: Programmed death-1 (PD-1) receptor-ligand interaction inhibits T cell activation against tumor cells. MK-3475 is a potent and highly selective humanized monoclonal antibody against PD-1 designed to directly block its interaction with its ligands, PD-L1 and PD-L2, thus removing the inhibition of T cell activation against cancer. MK-3475 led to prolonged anti-tumor activity in previously treated NSCLC patients. This Phase I study evaluated the safety, tolerability, and clinical activity of MK-3475 as initial therapy in patients with locally advanced or metastatic NSCLC. Methods: Patients with no prior systemic therapy for metastatic disease whose tumors expressed PD-L1 by a preliminary immunohistochemical assay were randomized to MK-3475 10 mg/kg every 2 or 3 wks (Q3W). The first 11 patients were randomized to 2 mg/kg and 10 mg/kg Q3W. At least 1 measurable tumor lesion, ECOG performance status of 0 to 1, adequate organ function and adequate tumor biopsy were required for enrollment. Prior adjuvant therapy was allowed if it preceded relapse by at least a year. Tumor response was assessed every 9 weeks until confirmed disease progression per immune related response criteria (irRC; investigator review); RECIST 1.1 by independent central review will also be performed. Results: 84 patients submitted tissue for PD-L1 assessment and 57 patients had tumors that expressed PD-L1. Between Feb 2013 and Oct 2013, 45 patients started treatment (n=6 2Q3W, n=23 10Q3W, n=16 10Q2W). Preliminary data indicate an ORR (confirmed and unconfirmed) of 36% (67% 2 mg/kg Q3W, 27% 10 mg/kg Q3W, 35% 10 mg/kg Q2W) by irRC. 25 patients (55%), including all but 2 responders, remain on treatment (treatment duration from 12+ to 48+ wks). 52% of patients experienced a drug-related adverse event (AE), usually grade 1-2 in severity, most commonly fatigue (14%), pruritus (8%), dermatitis acneiform (6%), diarrhea (6%) and dyspnea (6%). There was a single drug-related grade 3-5 AE, a grade 3 pericardial effusion. Conclusions: These data suggest that MK-3475 is generally well-tolerated and provides robust antitumor activity in a first-line setting in patients with locally advanced or metastatic NSCLC that expresses PD-L1. Clinical trial information: NCT01295827.