A phase II, open-label study of ramucirumab (IMC-1121B), an IgG1 fully human monoclonal antibody (MAb) targeting VEGFR-2, in combination with paclitaxel and carboplatin as first-line therapy in patients (pts) with stage IIIb/IV non-small cell lung cancer (NSCLC).

Abstract

7588 Background: VEGF-mediated angiogenesis contributes to NSCLC pathogenesis. Ramucirumab 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: Approximately 40 pts with advanced NSCLC (stage IIIB not suitable for locoregional therapy or stage IV) are planned for enrollment. Squamous histology and treated brain metastases are allowed. Exclusion criteria include prior bevacizumab, blood vessel invasion, intratumor cavitation, and recent gross hemoptysis. Pts receive ramucirumab 10 mg/kg, paclitaxel 200 mg/m2, and carboplatin AUC = 6 on Day 1 of each 3-week cycle for up to 6 cycles, followed by maintenance ramucirumab. Tumor evaluations occur every 6 weeks. The primary endpoint is progression free survival at 6 months; secondary/exploratory endpoints include safety, objective response rate (ORR), pharmacokinetic/pharmacodynamic profiles, and immunogenicity. Results: 31 pts have been enrolled to date, 22 are evaluable for safety (7M:15F; median age 59 [37-79]). None had squamous histology and 1 had treated brain metastases. 1 pt discontinued due to an adverse event (AE) (pneumothorax) and 2 pts reported serious AEs possibly related to ramucirumab: G4 febrile neutropenia and G2 pneumothorax. 15 pts are evaluable for best response. 10 of 15 pts had an objective response (1 complete response, 9 partial responses: ORR = 67%). 50% of responses have been confirmed, and in all cases, where repeat scans are available, initial response was confirmed. 5 of 15 pts had SD, 4 with tumor shrinkage. Preliminary median PFS is 5.7 m (95% CI: 5.62-5.75), with 14 of the 15 pts still on therapy as of December 4, 2009. Conclusions: Ramucirumab in combination with paclitaxel and carboplatin is well tolerated in NSCLC pts. Preliminary results do not highlight any unusual safety concerns. Preliminary efficacy data are encouraging. Updated safety and efficacy data and the relevance of pharmacodynamic markers to outcomes will be presented. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ImClone Systems ImClone Systems ImClone Systems