Safety of anti-EGFR necitumumab (neci) was evaluated in combination with anti-PD1 pembrolizumab (pembro) in pre-treated Stage IV NSCLC patients (pts).
Single-arm, multicenter Phase 1b study with expansion cohort to investigate the safety and effectiveness of neci combined with pembro in pts with Stage IV NSCLC. Part A: escalating doses of neci (600 mg and 800 mg IV) were administered on Day 1 and 8 every 3 weeks (Q3W) in combination with pembro (200 mg IV) on Day 1 Q3W. Part B: expansion cohort with neci at dose identified in Part A administered with pembro. Major eligibility criteria included progression after 1 platinum-based chemotherapy and ECOG PS 0-1. Tumor tissue was collected for analysis of biomarkers. Treatment continued until disease progression or unacceptable toxicity. We present data from an interim safety analysis conducted after the first 15 pts who received the recommended neci 800mg dose completed ≥2 cycles of treatment or discontinued early. All pts in Part A were included.
Part A completed without dose-limiting toxicity. As of 11 Feb 2016, 18 pts (neci 600 mg n = 3, 800 mg n = 15) were eligible for inclusion. Patients were female 44.4%, had median age 66.5 years [range 48-76], and adenocarcinoma histology 77.8%. All pts experienced ≥1 treatment-emergent adverse event (AE) with ≥1 related to study treatment. Four serious AEs occurred in 3 (16.7%) pts (all respiratory and mediastinal); none were treatment-related. No discontinuations or deaths were attributable to AEs. AEs occurring with >15% frequency are listed (table). Four (22.2%) pts experienced 8 grade >2 AEs: acute respiratory failure, hypokalaemia, hypophosphataemia, infusion-related reaction, pulmonary embolism, raised gamma-glutamyl transferase (1 pt each), and dyspnoea (2 pts).
Treatment-emergent AEs of frequency >15%, n (%)
|MedDRA preferred term||Interim safety population (N = 18)|
|Dermatitis acneiform||16 (88.9)|
|Dry skin||8 (44.4)|
|Appetite decreased||4 (22.2)|
|Respiratory tract infection||3 (16.7)|
The combination neci and pembro appears tolerable. The safety profile corresponds to individual profiles for both drugs, with no additive toxicities.
Clinical trial identification
Legal entity responsible for the study
Eli Lilly and Company
Eli Lilly and Company
B. Besse: Research funding: Puma Biotechnology, GlaxoSmithKline, AstraZeneca, Roche/Genentech, Clovis Oncology, Pfizer, Boehringer Ingelheim, Lilly, SERVIER, Onxeo, Bristol-Myers Squibb (BMS); expenses: Roche, Pfizer, BMS/Medarex, Novartis, Pierre Fabre. P. Garrido: Consulting or advisory roles: Roche, Novartis, Pfizer, Bristol-Myers Squibb (BMS), Boehringer Ingelheim (BI); speaker' bureau: Lilly, BMS, Novartis; expenses: BI, BMS, AstraZeneca. J. Bennouna: Advisory board and symposium presentation: Roche, Astra-Zeneca, Lilly, Boehringer-Ingelheim. J. Remon: Consultancy role: OESPharma. D. Planchard: Advisory Board : AstraZeneca, BMS, Clovis, GSK, Lilly, MSD, Pfizer, Roche, Sanofi, Pierre Fabre, Merck, Boehringer Ingelheim, Novartis. J. Raimbourg: Advisory board: BMS, Novartis and Roche. G.Y. Chao: Employed by Eli Lilly & Company. M. Gil: Employed: Eli Lilly & Company; Stocks: Eli Lilly & Company. All other authors have declared no conflicts of interest.