Daratumumab Plus Atezolizumab in Previously Treated Advanced or Metastatic Non‒Small-Cell Lung Cancer: Brief Report on a Randomized, Open-label, Phase 1b/2 Study (LUC2001 JNJ-54767414)

ABSTRACT Introduction The programmed death-ligand 1 (PD-L1) inhibitor atezolizumab improves progression-free survival (PFS) and overall survival (OS) for patients with previously treated advanced non‒small-cell lung cancer (NSCLC). Preclinical studies indicate that targeting CD38+ cells with daratumumab may synergistically enhance atezolizumab’s antitumor activity by increasing effector T-cell activity. Methods This phase 1b/2 study included safety run-in (1 cycle of daratumumab plus atezolizumab) and randomized phases (daratumumab plus atezolizumab vs atezolizumab alone). The primary objective of the randomized phase was to compare overall response rates (ORRs). Secondary objectives included evaluations of safety, clinical benefit rate (stable disease or better), PFS, OS, and pharmacokinetics. Results In total, 99 patients enrolled (safety run-in, n=7; randomized, n=46 per arm). In the randomized phase, the ORR was 4.3% for daratumumab plus atezolizumab and 13.0% for atezolizumab alone (odds ratio, 0.30; 95% confidence interval, 0.03-1.92). Respective clinical benefit rates were 52.2% and 43.5%. No improvements were observed in median PFS or median OS for combination therapy. The study was terminated because of limited efficacy of daratumumab plus atezolizumab. Conclusion Daratumumab plus atezolizumab therapy did not improve efficacy versus atezolizumab monotherapy for patients with previously treated advanced NSCLC.