a study of ramucirumab (ly3009806) or necitumumab (ly3012211) plus osimertinib in participants with lung cancer

Conditions: Non-small Cell Lung Cancer

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.

Keywords: t790m epidermal growth factor receptor (egfr)