Efficacy and Safety of Necitumumab and Pembrolizumab Combination Therapy in Advanced Non-Small Cell Lung Cancer with ≥50% PD-L1 Expression: A Nonrandomized Phase II Trial

Purpose: This study investigated the efficacy and safety of pembrolizumab and necitumumab as first-line therapy for patients with advanced non–small cell lung cancer (NSCLC) who had ≥50% programmed death-ligand 1 (PD-L1) expression. Patients and Methods: This nonrandomized, multicenter, openlabel, single-arm phase II trial included patients with previously untreated advanced NSCLC who had a PD-L1 tumor proportion score of ≥50%. Patients received pembrolizumab and necitumumab every 3 weeks for up to 35 cycles. The primary endpoint was the investigator-assessed objective response rate (ORR). The secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Results: The sample comprised 50 patients (38 men, 12 women; median age, 72 years; range, 51–90 years). The ORR was 76% (95% confidence interval, 61.9–86.9; P < 0.0001), with complete and partial response rates of 2% and 74%, respectively. Moreover, 10% and 8% of the patients had stable and progressive disease, respectively, whereas 6% could not be evaluated. The median PFS was 15.7 months, whereas the median OS was not reached at the time of analysis. The most common treatment-related adverse events were rash (64%) and hypomagnesemia (60%). Grade 3 interstitial lung disease occurred in five patients (10%), and grade 5 cardiac arrest occurred in one patient (2%). Conclusions: The pembrolizumab and necitumumab combination exhibited a promising ORR of 76% with a manageable safety profile in patients with NSCLC who had high PD-L1 expression. These findings highlight the need for further research on this regimen for patients with advanced NSCLC who have high PD-L1 expression.