P2.06-016 Phase 2 Study of Ramucirumab plus Weekly Docetaxel in Stage IV NSCLC Following Progression after Platinum-Based Chemotherapy: Topic: Phase II + NK

Ramucirumab, a human IgG1 monoclonal antibody, binds to vascular endothelial growth factor (VEGF) receptor 2, competing with VEGF-A, -C and –D and thereby preventing receptor activation and angiogenesis. The phase 3 REVEL trial demonstrated the addition of ramucirumab to docetaxel improved survival in patients with stage IV NSCLC following progression after platinum-based chemotherapy, independent of histology. The approved dose of docetaxel in NSCLC patients after progression on prior platinum-based chemotherapy is 75 mg/m2 every 3 weeks. The most common toxicity associated with this dosing regimen is myelosuppression, specifically neutropenia. In order to reduce the incidence of myelosuppression, various weekly docetaxel dosing regimens have been evaluated. These studies have suggested that weekly docetaxel can provide better tolerability with at least similar efficacy. This phase 2, single arm, open-label study (JVDN; NCT02831491) is designed to assess a potential reduction in the rate of grade ≥3 neutropenia and febrile neutropenia with weekly docetaxel in combination with ramucirumab, as compared to historical safety data from the REVEL trial. This study will also assess safety and efficacy of ramucirumab with weekly docetaxel in patients who received prior immunotherapy for NSCLC. Study JVDN includes patients (n=50) with stage IV NSCLC, with measurable disease and ECOG performance status 0-1 who have experienced disease progression from one prior platinum-based therapy which may have included bevacizumab. Prior immunotherapy for NSCLC is permitted. Patients will receive the approved ramucirumab dose regimen for NSCLC (10mg/kg IV) on day 1 every 3 weeks, followed by weekly docetaxel (35 mg/m2 IV) on days 1, 8 and 15 every 4 weeks. Treatment may continue until disease progression or a criterion for discontinuation is met. The primary endpoint is to assess safety, as measured by the rate of grade ≥3 neutropenia (CTCAE v4.0). Secondary endpoints for all patients include the rate of treatment-emergent febrile neutropenia, overall safety, pharmacokinetics (ramucirumab), and efficacy. Additional secondary endpoints of safety and efficacy will be assessed in patients who did or did not receive prior immunotherapy. An exploratory endpoint is to assess the association between biomarkers with safety and clinical outcomes. The primary and final analyses will occur after 31 and 50 patients, respectively, have completed ≥12 weeks of treatment to determine if grade ≥3 neutropenia and febrile neutropenia are reduced with the investigational weekly docetaxel treatment as compared to historical safety data from REVEL. Not applicable. Not applicable.