Clinical Trials /

Study of Safety and Efficacy of EGFR-TKI EGF816 in Combination With cMET Inhibitor INC280 in Non-small Cell Lung Cancer Patients With EGFR Mutation.

NCT02335944

Description:

The study is designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of EGF816 in combination with INC280 and to estimate the preliminary anti-tumor activity of EGF816 in combination with INC280 in patients with advanced non-small cell lung cancer (NSCLC) with documented EGFR mutation.

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

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Study of Safety and Efficacy of <span class="go-doc-concept go-doc-intervention">EGF816</span> in Combination With INC280 in Non-small Cell <span class="go-doc-concept go-doc-disease">Lung Cancer</span> Patients With <span class="go-doc-concept go-doc-biomarker">EGFR</span> <span class="go-doc-concept go-doc-keyword">Mutation</span>.

Title

  • Brief Title: Study of Safety and Efficacy of EGF816 in Combination With INC280 in Non-small Cell Lung Cancer Patients With EGFR Mutation.
  • Official Title: A Phase Ib/II, Multicenter, Open-label Study of EGF816 in Combination With INC280 in Adult Patients With EGFR Mutated Non-small Cell Lung Cancer.
  • Clinical Trial IDs

    NCT ID: NCT02335944

    ORG ID: CINC280X2105C

    NCI ID: 2014-000726-37

    Trial Conditions

    Non Small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    INC280 INC280 plus EGF816
    EGF816 INC280 plus EGF816

    Trial Purpose

    The study determines the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of
    EGF816 in combination with INC280 and to estimate the preliminary anti-tumor activity of
    EGF816 in combination with INC280 in patients with advanced non-small cell lung cancer
    (NSCLC) with documented EGFR mutation.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    INC280 plus EGF816 Experimental INC280, EGF816

    Eligibility Criteria

    Inclusion Criteria:

    - Patients with histologically documented, locally advanced or recurrent (stage IIIB
    who are not eligible for combined modality treatment) or metastatic (Stage IV)
    non-small cell lung cancer

    - Patients must have EGFR mutation L858R and/or ex19del

    - Presence of at least one measurable lesion according to RECIST v.1.1 as per Appendix
    1

    - ECOG performance status 2.

    - Phase Ib only: documented progression of disease according to RECIST v1.1 while on
    continuous treatment with EGFR TKI (e.g. erlotinib, gefitinib or afatinib, other EGFR
    TKIs may be allowed after discussion with Novartis)

    - Phase II Group 1 only: Patients with acquired resistance to EGFR TKI treatment
    defined as documented clinical benefit (CR (any duration), PR (any duration), or SD
    for at least 6 months) on prior EGFR TKI therapy (e.g. erlotinib, gefitinib or
    afatinib, other EGFR TKIs may be allowed after discussion with Novartis) who
    subsequently demonstrated progression according to RECIST v1.1

    - Phase II Group 2 only: Advanced NSCLC patients who have not been previously treated
    with any therapy known to inhibit EGFR and harbor de novo T790M mutation

    Exclusion Criteria:

    - Phase Ib and Phase II Group 1 only: Patients who have received more than one prior
    line of EGFR TKI therapy

    - Phase Ib and Phase II Group 1 only: Patients who have received more than three prior
    lines of antineoplastic therapy (including EGFR TKI) in the advanced setting

    - Phase II Group 2 only: Patients who have received more than two previous lines of
    antineoplastic therapies in advance setting

    - Phase II Group 2 only: Previous treatment with an investigational or marketed agent
    that inhibits EGFR. EGFR inhibitors include (but not limited to) erlotinib, gefitinib
    or other anti-EGFR or EGF monoclonal antibody therapy or dual TKI inhibitors

    - Previous treatment with a c-MET inhibitor or HGF-targeting therapy.

    - Patients with brain metastases

    - Patients have out of range laboratory values defined as

    - Absolute Neutrophil Count (ANC) <1.5 x 109/L

    - Hemoglobin (Hb) <9 g/dL

    - Platelets (PLT) <100 x 109/L

    - Total bilirubin >1.5 x upper limit of normal (ULN). For patients with Gilbert's
    syndrome total bilirubin >2.5 x ULN

    - AST and/or ALT >3 x ULN

    - Patients with tumor involvement of the liver must have AST and/or ALT >5 x ULN

    - Serum creatinine >1.5 x ULN

    - Measured or calculated creatinine clearance 45mL/min

    - Asymptomatic serum amylase and lipase > Grade 2

    - Serum amylase or serum lipase CTCAE grade 1 with signs and/or symptoms suggesting
    pancreatitis or pancreatic injury

    Other protocol-defined inclusion/exclusion criteria may apply.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Phase Ib : Incidence of dose limiting toxicities (DLTs)

    Phase II : objective response rate per RECIST v1.1

    Secondary Outcome Measures

    Number of participants with adverse events (AEs) and serious adverse events (SAEs)

    Safety of INC280 and EGF816

    Frequency of dose interruption, frequency of reduction and dose intensity

    objective response rate (phase Ib only)

    disease control rate

    progression free survival

    duration of response

    overall survival

    plasma concentration versus time profiles

    Area under the plasma concentration versus time curve (AUC) of EGF816

    Area under the plasma concentration versus time curve (AUC) of INC280

    Peak plasma concentration (Cmax) of INC280

    Peak plasma concentration (Cmax) of EGF816

    Elimination half life (t1/2) of INC280

    Elimination half life (t1/2) of EGF816

    Trial Keywords

    non small cell lung cancer,

    NSCLC,

    EGF816,

    INC280,

    tyrosine kinase inhibitor,

    c-MET