A Study of Ramucirumab (LY3009806) or Necitumumab (LY3012211) Plus Osimertinib in Participants With Lung Cancer
Condition: Non-small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Ramucirumab; Necitumumab; Osimertinib
Intervention description: Administered IV; Administered IV; Administered orally
Intervention MeSH terms: Osimertinib; Ramucirumab; Necitumumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: T790M; epidermal growth factor receptor (EGFR)

Summary:

      The main purpose of this study is to evaluate the safety of ramucirumab or necitumumab in
      combination with osimertinib in participants with non-small cell lung cancer (NSCLC).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have a diagnosis of NSCLC with at least 1 measurable lesion assessable using standard
             techniques by the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST
             1.1).

          -  Have T790M-positive status using a test validated and performed locally after disease
             progression on EGFR tyrosine kinase inhibitor (TKI) treatment.

          -  Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 at the
             time of enrollment.

          -  Have serum albumin that is ≥25 grams per liter at the time of enrollment.

          -  Have adequate organ function, with all screening labs performed within 7 days of
             treatment initiation.

          -  Have a life expectancy of ≥3 months.

          -  Have 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 (CTCAE) Version 4.0.

        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.

          -  Participants with symptomatic or growing brain metastases less than 4 weeks prior to
             enrollment.

          -  History of drug-induced interstitial lung disease (ILD), ILD, or radiation pneumonitis
             requiring treatment with steroid prior to study enrollment, or any evidence of
             clinically active ILD.

          -  Have a significant bleeding disorder or vasculitis or had a Grade ≥3 bleeding episode
             within 12 weeks prior to enrollment. Participants with a history of gross hemoptysis
             (defined as bright red blood of ≥1/2 teaspoon) within 2 months prior to enrollment are
             excluded.

          -  Have experienced any arterial thrombotic event or arterial thromboembolic event,
             including myocardial infarction, unstable angina (history or evidence of current
             clinically relevant coronary artery disease of current ≥Class III as defined by
             Canadian Cardiovascular Society Angina Grading Scale or congestive heart failure of
             current ≥Class III as defined by the New York Heart Association), cerebrovascular
             accident, or transient ischemic attack, within 6 months prior to enrollment.

          -  Have a history of deep vein thrombosis, pulmonary embolism, or any other significant
             venous thromboembolism (venous catheter thrombosis or superficial venous thrombosis
             not considered "significant") during the 3 months prior to study enrollment.
             Participants with venous thromboembolism occurring 3 to 6 months prior to study
             enrollment are allowed, if being treated with low molecular weight heparin.

          -  Have a history of gastrointestinal perforation and/or fistula within 6 months prior to
             enrollment.

          -  Have a bowel obstruction, history or presence of inflammatory enteropathy or extensive
             intestinal resection (hemicolectomy or extensive small intestine resection with
             chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea.

          -  Have uncontrolled hypertension, as defined in CTCAE Version 4.0, prior to initiating
             study treatment, despite antihypertensive intervention. CTCAE Version 4.0 defines
             uncontrolled hypertension as Grade >2 hypertension; clinically, the participant
             continues to experience elevated blood pressure (systolic >160 millimeters of mercury
             [mmHg] and/or diastolic >100 mmHg) despite medications.

          -  Are receiving chronic therapy with any of the following medications within 7 days
             prior to enrollment:

               -  nonsteroidal anti-inflammatory agents (NSAIDs; such as indomethacin, ibuprofen,
                  naproxen, or similar agents).

               -  other anti-platelet agents (such as clopidogrel, ticlopidine, dipyridamole, or
                  anagrelide).

          -  Have radiologically documented evidence of major blood vessel invasion or encasement
             by cancer.

          -  Have radiographic evidence of pulmonary intratumor cavitation, regardless of tumor
             histology.

          -  Are receiving concurrent treatment with other anticancer therapy, including other
             chemotherapy, immunotherapy, hormonal therapy, chemoembolization, or targeted therapy
             or radiotherapy treatment to more than 30% of the bone marrow or with a wide field of
             radiation within 4 weeks prior to enrollment.

          -  Have abnormal cardiac findings.

          -  Have undergone chest irradiation within 2 weeks prior to study drug administration,
             have not recovered from all radiation-related toxicities, or requires corticosteroids.
             A 2-week washout is permitted for focal palliative radiation to non-central nervous
             system disease.