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OA11 - Angiogenesis in Advanced Lung Cancer (ID 387)
- Event: WCLC 2016
- Type: Oral Session
- Track: Advanced NSCLC
- Presentations: 1
OA11.02 - Randomized Phase 1b/3 Study of Erlotinib plus Ramucirumab in First-Line EGFR Mut + Stage IV NSCLC: Phase 1b Safety Results (ID 3827)
11:00 - 12:30 | Author(s): P. Lee
Ramucirumab, an antiangiogenic IgG1 VEGFR2-targeted monoclonal antibody, and erlotinib, an EGFR tyrosine kinase inhibitor, are both active in advanced NSCLC. This global phase 1b/3 study (NCT02411448) will assess safety, tolerability and efficacy of the combination of ramucirumab with erlotinib in previously untreated patients with EGFR mutation-positive stage IV NSCLC. Here we report phase 1b safety results.
Eligible patients with ECOG PS 0-1, an activating EGFR mutation, and previously untreated stage IV NSCLC received ramucirumab 10 mg/kg intravenously on day 1 of repeating 14-day (± 3 days) cycle and erlotinib 150 mg orally daily. Treatment continued until disease progression or unacceptable toxicity. The primary objective of part A was to assess the safety and tolerability, in terms of dose limiting toxicities (DLT), of adding the recommended dose of ramucirumab for phase 3 (part B) to standard dose erlotinib. Data were analyzed separately for Japan (JP) (cohort 1) and US/EU (cohort 2). The DLT assessment occurred during the first 2 cycles (approximately 28 days).
As of Dec 16th, 2015, 14 patients were treated in the phase 1b part of this trial and 12 were DLT evaluable (6 JP; 6 US/EU). Overall, 6 grade (Gr) 3 treatment-emergent adverse events (TEAE) were noted, with at least one TEAE in 5 patients; no serious adverse events or Gr 4-5 TEAEs occurred. In the JP cohort the median age was 73 (64-79), 57% had ECOG PS 1 and 29% had a history of smoking. Four patients (57%) experienced a Gr 3 TEAE, of which one was a DLT (elevation of alanine aminotransferase) while the others (hypertension [n=2], dermatitis acneiform, and diarrhea) were not DLTs. In the US/EU cohort the median age was 71 (31-83), 86% had ECOG PS 1, and no patients had a history of smoking. One patient experienced Gr 3 TEAE of rash; no DLTs were observed in this cohort.
Enrollment on the phase 1b portion of this trial is complete and the safety results were consistent with previous combinations of antiangiogenic/erlotinib in this patient population. No unexpected toxicities were identified. Phase 3 enrollment has been initiated maintaining the dose of ramucirumab at 10 mg/kg Q2W.
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P2.06 - Poster Session with Presenters Present (ID 467)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
- Presentations: 1
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
P2.06-016 - Phase 2 Study of Ramucirumab plus Weekly Docetaxel in Stage IV NSCLC Following Progression after Platinum-Based Chemotherapy (ID 4614)
14:30 - 15:45 | Author(s): P. Lee
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.