Clinical Trials /

A Phase 1b/2 Study of Safety and Efficacy of Rociletinib in Combination With MPDL3280A in Patients With Advanced or Metastatic EGFR-mutant NSCLC

NCT02630186

Description:

This clinical research study is being carried out in two parts, Phase 1 and Phase 2. The primary purpose of the Phase 1 portion of the study is to observe the safety of the combination of rociletinib and MPDL3280A in EGFR-mutant NSCLC patients. The primary purpose of the Phase 2 portion of the study is to evaluate the safety and anti-tumor effects of the combination of rociletinib and MPDL3280A, at the best doses for the combination determined in Phase 1, in patients with EGFR-mutant NSCLC.

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

Completed

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

A <span class="go-doc-concept go-doc-intervention">Phase 1b</span>/2 Study of Safety and Efficacy of <span class="go-doc-concept go-doc-intervention">Rociletinib</span> in Combination With <span class="go-doc-concept go-doc-intervention">MPDL3280A</span> in Patients With Advanced or Metastatic <span class="go-doc-concept go-doc-biomarker">EGFR</span>-<span class="go-doc-concept go-doc-keyword">mutant</span> <span class="go-doc-concept go-doc-disease">NSCLC</span>

Title

  • Brief Title: A Phase 1b/2 Study of Safety and Efficacy of Rociletinib in Combination With MPDL3280A in Patients With Advanced or Metastatic EGFR-mutant NSCLC
  • Official Title: A Phase 1b/2 Study of the Safety and Efficacy of Rociletinib (CO-1686) Administered in Combination With MPDL3280A in Patients With Activating EGFR Mutation-positive (EGFRm) Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC)
  • Clinical Trial IDs

    NCT ID: NCT02630186

    ORG ID: CO-1686-032

    Trial Conditions

    Non-small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    Rociletinib CO-1686 Rociletinib and MPDL3280A
    MPDL3280A atezolizumab Rociletinib and MPDL3280A

    Trial Purpose

    This clinical research study is being carried out in two parts, Phase 1 and Phase 2. The
    primary purpose of the Phase 1 portion of the study is to observe the safety of the
    combination of rociletinib and MPDL3280A in EGFR-mutant NSCLC patients.

    The primary purpose of the Phase 2 portion of the study is to evaluate the safety and
    anti-tumor effects of the combination of rociletinib and MPDL3280A, at the best doses for
    the combination determined in Phase 1, in patients with EGFR-mutant NSCLC.

    Detailed Description

    This is a Phase 1b/2, open-label, non-randomized, multicenter study evaluating the safety
    and efficacy of rociletinib administered in combination with MPDL3280A.

    Phase 1: This will be the dose finding phase of the study. Patients will be enrolled to
    available Dosing Cohort. Patients who have progressed after prior first- or
    second-generation EGFR TKI, regardless of T790M mutation status, will be enrolled.

    Phase 2: Patients will be enrolled into 2 groups. Group A will enroll eligible first-line
    patients who are EGFR TKI treatment-nave and chemotherapy-nave. Group B will enroll
    eligible patients who have progressed after prior first- or second-generation EGFR TKI,
    regardless of T790M mutation status.

    Trial Arms

    Name Type Description Interventions
    Rociletinib and MPDL3280A Experimental Rociletinib, MPDL3280A

    Eligibility Criteria

    Inclusion Criteria:

    - ECOG performance status of 0 or 1

    - Adequate hematological and biological function, confirmed by defined laboratory
    values

    - Histologically or cytologically documented metastatic or unresectable, locally
    advanced or metastatic NSCLC, with one or more activating EGFR mutation (eg, G719X,
    exon 19 deletion, L858R, L861Q) and absence of exon 20 insertion

    - Measurable disease as defined by RECIST v1.1

    - Biopsy of tumor tissue for central evaluation, within 60 days prior to the first day
    of study treatment

    - For Phase 1 and Phase 2 Group B, progression after prior 1st or 2nd generation EGFR
    TKI (eg, erlotinib, gefitinib, afatinib). Previous chemotherapy for NSCLC is allowed.

    - For Phase 2 Group A, EGFR TKI treatment-nave and chemotherapy-nave

    Exclusion Criteria:

    - Unresolved toxicities from prior therapy

    - Symptomatic, untreated or unstable central nervous system or leptomeningeal
    metastases

    - Previous treatment with rociletinib or MPDL3280A, or other 3rd generation EGFR TKI
    (eg, AZD-9291, HM61713), or PD 1 axis targeted therapy (eg, anti PD 1 or anti-PD L1)

    - Prior treatment with CD137 agonists or other immune checkpoint blockade therapies,
    including anti-CTLA-4 therapeutic antibodies

    - Uncontrolled pleural effusion, pericardial effusion or ascites requiring recurrent
    drainage procedures

    - Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of
    bisphosphonate therapy or denosumab (bisphosphonate use for prevention of skeletal
    events allowed)

    - Known hypersensitivity to any component of the MPDL3280A or rociletinib formulations
    or history or hypersensitivity to chimeric humanized antibodies or fusion proteins

    - History of autoimmune disease

    - History of prior allogeneic hematopoietic stem cell transplantation or prior solid
    organ transplantation

    - Treatment with systemic immunosuppressive medications within 2 weeks prior to first
    day of study treatment (inhaled corticosteroids and mineralocorticoids allowed)

    - Live attenuated vaccine within 4 weeks prior to first day of study treatment

    - Active tuberculosis, active hepatitis, or positive HIV status

    - Class II to IV heart failure as defined by the New York Heart Association functional
    classification system

    - Untreated or uncontrolled cardiovascular disease or other symptomatic cardiac
    dysfunction

    - QTCF > 450 ms, inability to measure QT interval on ECG, personal or family history of
    long QT syndrome, requirement for medications that have the potential to prolong the
    QT interval

    - History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
    pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening
    chest computerized tomography (CT) scan (history of radiation pneumonitis in
    radiation field may be allowed)

    - Other malignancies within 5 years prior to enrollment, with the exception of
    carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized
    prostate cancer, or ductal carcinoma in situ

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Incidence of treatment-emergent adverse events, as assessed by NCI CTCAE v4.03

    Maximum concentration (Cmax) of rociletinib and its metabolites

    Time to maximum concentration (Tmax) for rociletinib and rociletinib metabolites

    Minimum concentration (Cmin) of rociletinib and metabolites

    Area under the curve (AUC) of rociletinib and rociletinib metabolites

    Maximum concentration (Cmax) of MPDL3280A

    Minimum concentration (Cmin) of MPDL3280A

    Objective response rate per RECIST v1.1 in Phase 2

    Secondary Outcome Measures

    Objective response rate per modified RECIST v1.1, incorporating immune-related criteria, in Phase 2

    Duration of response per RECIST v1.1 and modified RECIST v1.1, incorporating immune-related criteria, in Phase 2

    Progression-free survival per RECIST v1.1 and modified RECIST v1.1, incorporating immune-related criteria, in Phase 2

    Overall survival

    Longitudinal changes in blood based biomarkers (eg, mutations in EGFR) in ctDNA

    Trial Keywords