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A Study of MEHD7945A and Cobimetinib in Patients With Locally Advanced or Metastatic Cancers With Mutant KRAS

NCT01986166

Description:

This open-label, multicenter, global Phase Ib study will evaluate the safety, tolerability and pharmacokinetics of intravenous (IV) dosing of MEHD7945A in combination with oral dosing of cobimetinib in patients with locally advanced or metastatic solid tumors that carry a Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) mutation and for which standard therapies do not exist, have proven ineffective or intolerable or are considered inappropriate. The study comprises a dose-escalation (Stage 1) and an indication-specific cohort expansion stage (Stage 2).

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

A Study of <span class="go-doc-concept go-doc-intervention">MEHD7945A</span> and <span class="go-doc-concept go-doc-intervention">Cobimetinib</span> (GDC-0973) in Patients With Locally Advanced or Metastatic Cancers With <span class="go-doc-concept go-doc-keyword">Mutant</span> <span class="go-doc-concept go-doc-biomarker">KRAS</span>

Title

  • Brief Title: A Study of MEHD7945A and Cobimetinib (GDC-0973) in Patients With Locally Advanced or Metastatic Cancers With Mutant KRAS
  • Official Title: A PHASE Ib, OPEN-LABEL, DOSE-ESCALATION STUDY OF THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF MEHD7945A and GDC-0973 IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC SOLID TUMORS WITH MUTANT KRAS
  • Clinical Trial IDs

    NCT ID: NCT01986166

    ORG ID: GO29030

    NCI ID: 2013-001910-14

    Trial Conditions

    Neoplasms

    Trial Interventions

    Drug Synonyms Arms
    MEHD7945A MEHD7945A + cobimetinib
    cobimetinib MEHD7945A + cobimetinib

    Trial Purpose

    This open-label, multicenter, global Phase Ib study will evaluate the safety, tolerability
    and pharmacokinetics of MEHD7945A in combination with cobimetinib (GDC-0973) in patients
    with locally advanced or metastatic solid tumors that carry a KRAS mutation. The study
    comprises a dose-escalation and an indication-specific cohort expansion stage. Cohorts of
    patients will receive MEHD7945A intravenously every two weeks and escalating doses of oral
    cobimetinib for 21 consecutive days followed by 7 days off (28-day cycle). Study treatment
    may be continued until disease progression or unacceptable toxicity occurs.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    MEHD7945A + cobimetinib Experimental MEHD7945A, cobimetinib

    Eligibility Criteria

    Inclusion Criteria:

    - Locally advanced or metastatic solid KRAS-mutant tumors, for which standard therapies
    do not exist, have proven ineffective or intolerable or are considered inappropriate

    - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

    - Evaluable disease or disease measurable per modified RECIST v1.1

    - Consent to provide archival tumor tissue for biomarker testing

    - Additionally, for patients who are considered for enrollment into the indication
    specific expansion cohorts in Stage 2, the current cancer must be either KRAS-mutant
    colorectal cancer (CRC) or KRAS-mutant non-small cell lung cancer (NSCLC)

    Exclusion Criteria:

    - History of prior significant toxicity from another MEK pathway inhibitor or
    combination of another MEK and EGFR inhibitor requiring discontinuation of treatment

    - Previous treatment with a combination of a MEK inhibitor with an EGFR inhibitor
    (applies only to the indication specific expansion cohorts in Stage 2)

    - Allergy or hypersensitivity to components of the cobimetinib formulations

    - History of severe (Grade 3 or 4) allergic or hypersensitivity reaction to therapeutic
    antibodies that required discontinuation of therapy

    - History of interstitial lung disease (ILD)

    - Known severe ulcer disease

    - History of or evidence of retinal pathology on ophthalmologic examination that is
    considered a risk factor for neurosensory retinal detachment, CSCR, RVO, or
    neovascular macular degeneration.

    Patients will be excluded if they currently have either of the following conditions which
    have been identified as risk factors for CSCR:

    - Uncontrolled glaucoma with intraocular pressure >21 mmHg

    - Grade >/= 3 hypertriglyceridemia.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Safety: Incidence, nature and severity of adverse events

    Safety: Incidence of anti-MEHD7945A antibodies

    Safety: Incidence and nature of dose-limiting toxicities (DLTs)

    Secondary Outcome Measures

    Pharmacokinetics: MEHD7945A maximum serum concentrations (Cmax)

    Pharmacokinetics: MEHD7945A minimum serum concentrations (Cmin)

    Pharmacokinetics: Cobimetinib area under the concentration-time curve (AUC)

    Pharmacokinetics: Cobimetinib maximum plasma concentrations (Cmax)

    Pharmacokinetics: Time to maximum cobimetinib plasma concentration (tmax)

    Objective response, defined as a complete or partial response >/= 4 weeks after the initial documentation

    Duration of objective response

    Progression-free survival

    Trial Keywords