Phase 2 Trial Update of Ramucirumab for NSCLC

Lilly announced new data from two Phase 2 ramucirumab (IMC-1121B) trials in patients with non-small cell lung cancer (NSCLC).

A randomized open-label Phase 2 study of 140 chemotherapy-naive patients investigated ramucirumab in combination with first-line chemotherapy in advanced nonsquamous NSCLC. Patients were randomized based on histology (nonsquamous [Arms A vs. B]; squamous [Arms C vs. D]). Enrollment of patients with squamous histology [Arms C vs. D] is ongoing. Therapy in Arm A included Lilly's Alimta (pemetrexed; 500mg/m2) plus carboplatin (AUC=6) or cisplatin (75mg/m2) once every three weeks, while therapy in Arm B included ramucirumab (10mg/kg), Alimta (500mg/m2) plus carboplatin (AUC=6) or cisplatin (75 mg/m2) once every three weeks.

The primary endpoint for the interim analysis was PFS. Other interim endpoints included change in tumor size, disease control rate (DCR), and safety. Interim median PFS, based on a pre-specified analysis, was 4.3 months for Arm A, the control arm, and 6.3 months for Arm B, the experimental arm (hazard ratio, 0.48; 90% CI: 0.31-0.74). DCR was 72% for Arm A and 87% for Arm B. 

An additional Phase 2 open-label study investigated ramucirumab in combination with paclitaxel (Taxol; Bristol-Myers Squibb) and carboplatin as first-line therapy in patients with advanced NSCLC. Patients with squamous histology and treated brain metastases were allowed. Forty patients received treatment, receiving ramucirumab (10mg/kg), paclitaxel (200mg/m2) and carboplatin (AUC=6) on day one of a three-week cycle for up to six cycles, followed by maintenance ramucirumab.

The primary endpoint was PFS at six months. Secondary/exploratory endpoints were safety, overall response rate, overall survival rate at one year, pharmacokinetic and pharmacodynamic (PK/PD) profiles and immunogenicity. The overall DCR (CR+PR+SD) reached 90% and PFS at six months was 59% (95% CI = 41.3%-72.9%). Median PFS was 7.85 months.

Ramucirumab is a fully human IgG1 monoclonal antibody receptor antagonist designed to bind the extracellular domain of vascular endothelial growth factor (VEGF) receptor-2, thereby blocking the interaction of VEGF ligands (VEGF-A, VEGF-C, and VEGF-D) and inhibiting receptor activation. VEGF receptor 2 is considered a primary mediator of angiogenesis. When activated by VEGF ligands, VEGF receptor 2 promotes endothelial cell proliferation and survival, migration, and vascular permeability.

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