Randomized phase 1b/3 study of erlotinib plus ramucirumab in first-line EGFR mut + stage IV NSCLC: phase 1b safety results

Abstract

Background: 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. Methods: 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). Results: 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. Conclusion: 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.