Anti-PD-1 antibody cetrelimab (JNJ-63723283) in patients with advanced cancers: Updated phase I/II study results.

Abstract

31 Background: Cetrelimab (JNJ-63723283) is an IgG4, anti-programmed cell death protein-1 (PD-1) antibody. Here we present updated results from an ongoing phase 1/2 study of cetrelimab in patients (pts) with advanced or refractory solid cancers. Methods: Part 2 of the study evaluated safety and efficacy of cetrelimab at 240 mg Q2W, a recommended phase 2 dose selected in Part 1 (Calvo JCO 2018; 36 suppl 5:58). Tumor types for Part 2 included non-small cell lung cancer (NSCLC), melanoma (MEL), bladder, renal cell, small cell lung cancer (SCLC), microsatellite-high (MSI-H)/DNA mismatch repair deficient (dMMR; locally or centrally tested) colorectal cancer (CRC) and gastric/esophageal cancer (GCA/EC). Tumor response was assessed by the investigator following RECIST v1.1. Results: As of 3 Sep 2018, 192 pts have been treated with cetrelimab from 80–800 mg Q2W and 480 mg Q4W. Median age was 60 years (23–86), and median prior regimens was 2 (1–12). Median duration of treatment was 85 days (1–561); 82 pts remain on treatment. Full receptor occupancy was maintained throughout dosing interval. Most common adverse events (AEs) were asthenia (19%), fatigue (19%), dyspnea (16%) and diarrhea (16%). Grade ≥3 AEs, regardless of causality, were reported in 45% of pts; most common were anemia (6%), dyspnea (4%), increased ALT (3%) and increased AST (3%). Observed serious AEs were dyspnea (4%), pleural effusion and intestinal obstruction (3% each). All grade and grade ≥3 immune-related AEs were reported in 30% and 7% of pts, respectively. Among response-evaluable pts (n = 156) from Parts 1 and 2, overall response rate (ORR) was 15%, with 2 complete and 22 partial responses. Half of pts had stable disease or better. ORR was 26% (7/27) in NSCLC (42% [5/12] in PD-L1+ NSCLC [≥50% by IHC]), 25% (12/49) in MEL (28% [12/43] in non-uveal MEL), 50% (1/2) in renal cancer, 8% (2/26) in MSI-H/dMMR CRC (recruited later per amendment) and 14% (2/14) in GCA/EC. No responses were observed in bladder cancer (n = 4) or SCLC (n = 10). Conclusions: The safety profile and preliminary activity of cetrelimab in immune-sensitive advanced cancers is consistent with known PD-1 inhibitors. The study is ongoing and analysis by PD-L1 status will be reported later. Clinical trial information: NCT02908906.