Trials of anti-EGFR necitumumab (neci) and the CDK4 and CDK6 inhibitor abemaciclib have demonstrated anti-tumor activity of each agent in patients with NSCLC.
Single-arm, multicenter Phase 1b expansion cohort study to investigate the effectiveness, safety and tolerability of neci combined with abemaciclib in ∼70 patients with Stage IV NSCLC (NCT02411591). Part A: escalating doses of abemaciclib (100 mg, 150 mg, and 200 mg oral) are administered on a continuous schedule every 12 hours on days 1–21 in combination with neci (800 mg IV) on days 1 and 8, every 21 days. Part B: abemaciclib dose identified in Part A is administered with neci in squamous (sq) and non-sq NSCLC patients. Major eligibility criteria include: progression after platinum-based chemotherapy and 1 other prior chemotherapy for advanced and/or metastatic disease; ECOG PS 0-1; no symptomatic brain metastases. Patients with prior treatment with CDK4- or CDK6-targeting agents or neci are excluded. Tumor tissue is collected for investigation of NSCLC biomarkers including KRAS mutation and EGFR expression. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of consent by the patient. The objectives of the study are to evaluate tolerability and the efficacy of combination therapy in terms of progression-free survival rate at 3 months. Secondary objectives include overall survival, overall response rate (ORR) and disease control rate (DCR). The ORR and DCR denominator includes each patient enrolled who receives either study drug, who has complete radiographic assessment at baseline, and ≥1 complete radiographic assessment post-baseline. The ORR numerator includes patients counted in the denominator with a best overall tumor response (partial/complete response); the DCR numerator also includes stable disease. The Kaplan-Meier method will estimate parameters for time-to-event variables. Part A has fully enrolled (n = 15) with one dose-limiting toxicity (DLT) at abemaciclib 150mg. DLT evaluation of the 200mg abemaciclib cohort will identify recommended dosing for Part B.
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. F. Barlesi: Honoraria: Lilly Oncology, Consulting or advisory: Lilly Oncology. M. Ceccarelli: Employment: Eli Lilly and Company; Stock: Eli Lilly and Company. G.Y. Chao: Employment: Eli Lilly and Company. B. Frimodt-Moller, M. Gil: Employment: Eli Lilly and Company; Stocks: Eli Lilly and Company. J. Vansteenkiste: Consulting or advisory roles: Novartis, Boehringer Ingelheim, Lilly, MSD Oncology, AstraZeneca; Research funding: AstraZeneca.