Phase 1  



VEGF Receptor-2 Antagonist

An Open-Label, Multicenter, Phase 1 Study With Expansion Cohorts of Ramucirumab or Necitumumab in Combination With Osimertinib in Patients With Advanced T790M-Positive EGFR-Mutant Non-small Cell Lung Cancer After Progression on First-line EGFR TKI Therapy*

show modal icon NCT02789345
Key Inclusion Criteria
  • Diagnosis of non-small cell lung cancer (NSCLC) with measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
  • Known T790M-positive status using a test validated and performed locally after disease progression on EGFR tyrosine kinase inhibitor (TKI)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Serum albumin that is ≥25 g/L
  • Adequate organ function, with all screening labs performed within 7 days of treatment initiation
  • Life expectancy of ≥3 months
  • Resolution, except where otherwise stated in the inclusion criteria, of all clinically significant toxic effects of prior systemic cancer therapy, surgery, or radiotherapy to grade ≤1 by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0

Key Exclusion Criteria
  • Previous treatment with an EGFR monoclonal antibody (except for past treatment for squamous cell carcinoma of head and neck or metastatic colorectal cancer)
  • Previous treatment with osimertinib or third-generation EGFR TKIs
  • Symptomatic or growing brain metastases <4 weeks prior to enrollment
  • History of drug-induced interstitial lung disease (ILD), ILD, or radiation pneumonitis requiring treatment with steroid, or any evidence of clinically active ILD
  • Significant bleeding disorder or vasculitis, or had a grade ≥3 bleeding episode within 12 weeks prior to enrollment
  • Any arterial thrombotic event or arterial thromboembolic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to enrollment
  • History of deep vein thrombosis, pulmonary embolism, or any other significant venous thromboembolism during the 3 months prior to study enrollment
  • History of gastrointestinal perforation and/or fistula within 6 months prior to enrollment
  • Bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection, Crohn's disease, ulcerative colitis, or chronic diarrhea
  • Uncontrolled hypertension as defined in CTCAE version 4.0
  • Receiving chronic therapy with nonsteroidal anti-inflammatory or antiplatelet agents within 7 days prior to enrollment
  • Radiologically documented evidence of major blood vessel invasion or encasement by cancer, or radiographic evidence of pulmonary intratumor cavitation
  • Receiving concurrent treatment with another anticancer therapy
  • Underwent chest irradiation within 2 weeks prior to study drug administration, have not recovered from all radiation-related toxicities, or requires corticosteroids

This clinical trial is being conducted globally. 
Ramucirumab is administered intravenously (IV) on day 1 Q2W and osimertinib is administered PO QD during each 14-day cycle.
Necitumumab is administered IV on days 1 and 8 Q3W and osimertinib is given PO QD during each 21-day cycle.
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The safety and efficacy of the agents under investigation have not been established. There is no guarantee that the agents will receive regulatory approval and become commercially available for the uses being investigated.