Clinical Trials /

A Phase I/II, Multicenter, Open-label Study of EGFRmut-TKI EGF816, Administered Orally in Adult Patients With EGFRmut Solid Malignancies

NCT02108964

Description:

To estimate the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) (Phase l part) of EGF816 and to investigate the anti-tumor activity of EGF816 (Phase II part).

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

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

A Phase I/II, Multicenter, Open-label Study of EGFRmut-<span class="go-doc-concept go-doc-intervention">TKI</span> <span class="go-doc-concept go-doc-intervention">EGF816</span>, Administered Orally in Adult Patients With EGFRmut Solid Malignancies

Title

  • Brief Title: A Phase I/II, Multicenter, Open-label Study of EGFRmut-TKI EGF816, Administered Orally in Adult Patients With EGFRmut Solid Malignancies
  • Official Title: A Phase I/II, Multicenter, Open-label Study of EGFRmut-TKI EGF816, Administered Orally in Adult Patients With EGFRmut Solid Malignancies
  • Clinical Trial IDs

    NCT ID: NCT02108964

    ORG ID: CEGF816X2101

    Trial Conditions

    NSCLC

    Trial Interventions

    Drug Synonyms Arms
    EGF816 Phase I part, Phase II part arm 1, Phase II part arm 2, Phase II part arm 3, Phase II part arm 4

    Trial Purpose

    To estimate the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of EGF816
    and to investigate the anti-tumor activity of EGF816

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Phase I part Experimental at least 21 patients with EGFR T790 mutations EGF816
    Phase II part arm 1 Experimental 20 patients must have advanced NSCLC with EGFR mutation (L858R or ex19del, not T790M) EGF816
    Phase II part arm 2 Experimental 80 patients must have advanced NSCLC with an acquired T790M EGFR mutation EGF816
    Phase II part arm 3 Experimental 80 patients must have advanced NSCLC with a "de novo" T790M EGFR mutation EGF816
    Phase II part arm 4 Experimental 10 patients must have an advanced solid tumor harboring any EGFR mutation; and NOT be otherwise eligible for groups 1-3 EGF816

    Eligibility Criteria

    Inclusion Criteria:

    - Written informed consent must be obtained prior to any screening procedures

    Phase I part only:

    - Patient must have an advanced NSCLC with any documented EGFR T790 mutation.

    Phase II part only:

    - Group 1: patients must have advanced NSCLC with EGFR mutation (L858R or ex19del, not
    T790M)

    - Group 2: patients must have advanced NSCLC with an acquired T790M EGFR mutation

    - Group 3: patients must have advanced NSCLC with a "de novo" T790M EGFR mutation.

    - Group 4: patients must have an advanced solid tumor harboring any EGFR mutation; and
    NOT be otherwise eligible for groups 1-3

    - ECOG performance status 2

    - Presence of at least one measurable lesion according to RECIST v1.1

    Exclusion Criteria:

    Phase I part only:

    - Patient have received more than 3 previousanti-neoplastic therapies in the advanced
    setting

    Phase II part only:

    - Group 1:No limitation of previous anti-neoplastic treatments in the advanced setting

    - Group 2: More than total of 2 previous anti-neoplastic therapies in the advanced
    setting

    - Group 3: More than total of 2 previous anti-neoplastic therapies in the advanced
    setting

    - Group 4: No limitation of previous anti-neoplastic treatments in the advanced
    setting.

    - Patients with brain metastases

    - Any medical condition that would, in the investigator's judgment, prevent the
    patient's participation in the clinical study due to safety concerns or compliance
    with clinical study procedures.

    - Patient have out of range laboratory values defined as

    - Bone marrow function

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

    - Hemoglobin (Hgb) <9 g/dL

    - Platelets <100 x 109/L

    - Hepatic and renal function

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

    - Aspartate aminotransferase (AST) and/or alanine aminotransferase (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 and/or measured creatinine clearance < 75% LLN

    - Patients receiving treatment with medications that are known to be 1) strong
    inhibitors or inducers of CYP3A4/5; 2) CYP2D6 substrate with narrow therapeutic index

    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 I Part: Incidence of dose limiting toxicity (DLT)

    Phase II Part: Overall response rate (ORR)

    Secondary Outcome Measures

    Best overall response

    Progression-free survival

    Duration of response

    Frequency/severity of adverse events (AEs)

    Pharmacokinetics properties of EGF816 and metabolite LMI258

    the tumor EGFR signaling inhibition by EGF816

    Number of Dose interruptions and reductions

    Frequency/severity of serious adverse events (SAEs)

    Trial Keywords

    NSCLC,

    EGFRmut -TKI,

    EGF816,

    EGFRmut solid malignancies