Final Results of a Phase 2, Open-Label Study of Ramucirumab (IMC-1121B; RAM), an IGG1 MAB Targeting Vegfr-2, with Paclitaxel and Carboplatin as First-Line Therapy in Patients (PTS) with Stage IIIB/IV Non-Small Cell Lung Cancer (NSCLC) (NCT00735696)

ABSTRACT Background VEGF-mediated angiogenesis contributes to NSCLC pathogenesis. RAM is a recombinant human mAb that binds the extracellular domain of the vascular endothelial growth factor receptor-2 (VEGFR-2) and inhibits cancer growth in diverse preclinical models. Methods Pts with advanced NSCLC (Stage IIIb not suitable for locoregional therapy or Stage IV) were eligible. Squamous histology and treated brain metastases were allowed. Exclusion criteria included prior bevacizumab, blood vessel invasion, intratumor cavitation, and recent gross hemoptysis. Pts received RAM 10 mg/kg, paclitaxel 200 mg/m2, and carboplatin AUC = 6 on Day 1 of a 3-week cycle for up to 6 cycles, followed by maintenance RAM. The primary endpoint was PFS at 6 months (m); secondary/exploratory endpoints were safety, ORR, OS rate at 1 year, PK/PD profiles, and immunogenicity. Results 40 pts were treated (15M:25F; median age 60; 39 nonsquamous / 1 squamous); all have discontinued. 39 pts were evaluable for response. 22 of 40 treated pts had an objective response (1 CR, 21 PR; ORR = 55%). 14 pts had a best response of SD. Median PFS was 7.85 m (95% CI: 5.49 m-9.86 m), and the PFS rate at 6 m was 62.5% (90% CI: 48.3%-75.3%); the 1-year survival rate was 74.6% (95% CI: 57.9%-85.4%). 34 of 40 pts (85%) reported an AE at least possibly related to RAM; the most common related AEs were fatigue (53%), peripheral neuropathy (33%), nausea (28%), myalgia (23%), and epistaxis (23%). Related AEs of Gr ≥ 3 were reported for 15 pts; the most common were neutropenia (5 pts), thrombocytopenia (4 pts), fatigue, febrile neutropenia (3 pts each), peripheral neuropathy and pulmonary embolism (2 pts each). There were 5 pts with a total of 6 Gr 4 related events: febrile neutropenia, pulmonary embolism (2 pts each), neutropenia and thrombocytopenia (1 pt each). Conclusions RAM in combination with paclitaxel and carboplatin shows promising efficacy based on the overall disease control rate (CR + PR + SD) reaching 90% and PFS rate at 6 m of 62.5%, and is well tolerated by patients with NSCLC. Disclosure D.R. Camidge: I have received research funding from Eli Lilly and Company and honoraria from ImClone Systems. R.C. Doebele: Research Funding: ImClone Systems, Eli Lilly u0026 Co., Pfizer Inc. Honoraria: Boehringer Ingelheim, Abbott Laboratories, Pfizer Inc Stock: Ariad ( M. Ballas: I now have an employment position at Bristol Myers Squibb (BMS), own T. Jahan: I have received additional research funding from Eli Lilly u0026 Co. for other trials, as well as research funding from Morphotek, Pfizer, and Genentech. I have no speaker or consultant income to disclose. S. Yurasov: Employed by ImClone/Eli Lilly; own Lilly stock. All other authors have declared no conflicts of interest.