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A Study of Ramucirumab (LY3009806) or Necitumumab (LY3012211) Plus Osimertinib in Participants With Lung Cancer

NCT02789345

Description:

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).

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

A Study of <span class="go-doc-concept go-doc-intervention">Ramucirumab</span> (LY3009806) or Necitumumab (LY3012211) Plus <span class="go-doc-concept go-doc-intervention">Osimertinib</span> in Participants With Lung Cancer

Title

  • Brief Title: A Study of Ramucirumab (LY3009806) or Necitumumab (LY3012211) Plus Osimertinib in Participants With Lung Cancer
  • Official Title: 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
  • Clinical Trial IDs

    NCT ID: NCT02789345

    ORG ID: 16357

    NCI ID: I4T-MC-JVDL

    Trial Conditions

    Non-small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    Ramucirumab LY3009806 Ramucirumab + Osimertinib
    Necitumumab LY3012211 Necitumumab + Osimertinib
    Osimertinib AZD9291 Ramucirumab + Osimertinib, Necitumumab + Osimertinib

    Trial Purpose

    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).

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Ramucirumab + Osimertinib Experimental Dose Finding: Ramucirumab given intravenously (IV) on day 1 every 2 weeks (Q2W) and osimertinib given orally daily during each 14 day cycle. Expansion: Ramucirumab given IV on day 1 Q2W and osimertinib given orally daily during each 14 day cycle. Ramucirumab, Osimertinib
    Necitumumab + Osimertinib Experimental Dose Finding: Necitumumab given IV on days 1 and 8 every 3 weeks (Q3W) and osimertinib given orally daily during each 21 day cycle. Expansion: Necitumumab given IV on days 1 and 8 Q3W and osimertinib given orally daily during each 21 day cycle. Necitumumab, Osimertinib

    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.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Number of Participants with Dose Limiting Toxicities (DLTs)

    Secondary Outcome Measures

    Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab

    PK: Cmin of Necitumumab

    Objective Response Rate (ORR): Percentage of Participants with a Complete Response (CR) or Partial Response (PR)

    Disease Control Rate (DCR): Percentage of Participants with CR, PR or Stable Disease (SD)

    Duration of Response (DoR)

    Progression Free Survival (PFS)

    Overall Survival (OS)

    Trial Keywords

    T790M

    epidermal growth factor receptor (EGFR)