Hallmarks of tumor growth include angiogenesis and immunosuppression, and combining R (anti-vascular endothelial growth factor receptor 2 antibody) with D(anti-programmed death ligand-1 antibody) to target both processes demonstrates synergy in preclinical models. This global phase 1 trial (NCT02572687) will assess safety, toxicities, pharmacokinetics, immunogenicity, and preliminary efficacy of the combination in pts with locally advanced and unresectable or metastatic G/GEJ adenocarcinoma, NSCLC, or HCC.
Key inclusion criteria include pts who have progressed on therapies, can provide a tumor biopsy sample, and have an ECOG PS of 0-1. Two combination dose/schedules will be evaluated in the Phase 1A/dose limiting toxicity (DLT) observation phase, following 6 + 3 dose de-escalation with a starting dose of R (10 mg/kg intravenous [IV]) and D (1125mg IV) Q3W for NSCLC and R (8 mg/kg IV) and D (750 mg IV) Q2W for G/GEJ and HCC (1 treatment cycle [21 days for the NSCLC cohort and 28 days for the Gastric-GEJ and HCC cohorts]). Phase 1A will include 18-54 pts. After the Phase 1A/DLT evaluation, each cohort will be expanded to approximately 20 pts who will receive study treatment until confirmed disease progression or unacceptable toxicity (Phase 1B). A final analysis will be performed 12 months after the last patient's first dose of study treatment. The primary objective is the assessment of the safety and tolerability of the combination of R + D, and the secondary objectives are pharmacokinetics (Phase 1A/1B) and preliminary efficacy and immunogenicity (Phase 1B). Interim analyses will occur after all pts within a cohort have completed (or discontinued from) approximately 24 weeks of treatment.
Clinical trial identification
Legal entity responsible for the study
Eli Lilly and Company
Eli Lilly and Company
Y-J. Bang: Research fundings (through the institution) from Lilly, and consulting roles of Lilly.L.W. Goff: Advisory role for Celgene; research funding from Astellas Pharma, Pfizer, Onyx, Sun Pharma, Lilly, and Bristol-Myers Squibb. H. Wasserstrom, J. Yang, G. Mi: Employee of Eli Lilly and Company and holds equity in the company. M. Reck: Advisory role for Roche, Lilly, Bristol-Myers Squibb, AstraZeneca, Pfizer, Boehringer-Ingelheim, and Celgene. All other authors have declared no conflicts of interest.