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:

This is a Phase I/II, multi-center, open-label study, composed with a Phase I part (dose-escalation phase) followed by a Phase II part (expansion phase). The dose escalation phase was designed to determine as primary objective the maximum tolerated dose (MTD) or recommended Phase II dose (RP2D) of EGF816 monotherapy in adult subjects with locally advanced (stage IIIB) or metastatic (stage IV) NSCLC harboring specific EGFR mutations. Patients may have or not have received prior lines of antineoplastic therapy. An adaptive Bayesian Logistic Regression Model (BLRM) employing the escalation with overdose control (EWOC) principle will be used during the dose escalation part for dose level selection and MTD recommendation. The primary objective of the Phase II part is to estimate antitumor activity of EGF816 as measured by overall response rate (ORR) determined by Blinded Independent Review Committee (BIRC) assessment in accordance to RECIST 1.1.

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