A Study of Ramucirumab (LY3009806) in Combination With Erlotinib in Previously Untreated Participants With EGFR Mutation-Positive Metastatic NSCLC (RELAY)
Condition: Metastatic Non-Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Ramucirumab; Placebo; Erlotinib; Gefitinib; Osimertinib
Intervention description: Administered IV.; Administered IV.; Administered orally.; Administered orally.; Administered orally.
Intervention MeSH terms: Erlotinib Hydrochloride; Gefitinib; Osimertinib; Ramucirumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 545.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The main purpose of this study is to evaluate the efficacy and safety of ramucirumab in
      combination with erlotinib as compared to placebo in combination with erlotinib in previously
      untreated participants with stage IV non-small cell lung cancer (NSCLC) harboring an
      activating epidermal growth factor receptor (EGFR) mutation (Exon 19-Del and Exon 21 L858R).
      Safety and tolerability of ramucirumab in combination with erlotinib will be assessed in Part
      A before proceeding to Part B.

      The purpose of Part C is to determine the efficacy and safety of ramucirumab in combination
      with gefitinib in previously untreated East Asian participants with EGFR mutation-positive
      metastatic NSCLC and of ramucirumab in combination with osimertinib in those participants
      whose disease progressed on ramucirumab and gefitinib and that have T790M - positive
      metastatic NSCLC.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Cytologically or histologically confirmed diagnosis of Stage IV NSCLC as defined by
             the American Joint Committee on Cancer Staging Criteria for Lung Cancer (AJCC 7th
             edition 2009).

          -  Eligible for first-line treatment with erlotinib based on documented evidence of tumor
             harboring an activating EGFR mutation [exon 19 deletion or exon 21 (L858R)
             substitution mutation].

          -  Mandatory provision of adequate archived stage IV NSCLC tissue samples or tissue
             samples other than stage IV NSCLC may be acceptable (optional for part C).

          -  At least one measurable lesion.

          -  Life expectancy of at least 3 months.

        Exclusion Criteria:

          -  Known T790M EGFR mutation (not applicable for Part C Period 2).

          -  Known leptomeningeal carcinomatosis, uncontrolled/unstable spinal cord compression, or
             brain metastases.

          -  Serious illness or medical condition.

          -  Ongoing treatment with CYP3A4 inducers or strong inhibitors.

          -  Ongoing therapy with nonsteroidal anti-inflammatory drugs for more than 2 months.

          -  History of gross hemoptysis.

          -  Significant bleeding disorders.

          -  Radiologically documented evidence of major blood vessel invasion or encasement by
             cancer.

          -  Radiographic evidence of intratumor cavitation.

          -  History of gastrointestinal perforation within last 6 months.

          -  History of bowel obstruction, inflammatory enteropathy or extensive intestinal
             resection.

          -  History of any arterial thrombotic event within 6 months prior to enrollment.

          -  The participant has any known significant ophthalmologic abnormalities of the surface
             of the eye.