Clinical Trials /

A Phase 1b Study of Atezolizumab in Combination With Erlotinib or Alectinib in Participants With Non-Small Cell Lung Cancer (NSCLC)

NCT02013219

Description:

This open-label, multicenter study will assess the safety, tolerability, and pharmacokinetics of intravenous (IV) dosing of atezolizumab in combination with oral erlotinib or alectinib in participants with NSCLC. This study has two stages. In the erlotinib group, the combination treatment will be given to participants with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-treatment-naive, advanced (nonresectable) NSCLC in a safety-evaluation stage and to participants with previously untreated EGFR mutation-positive, advanced NSCLC in an expansion stage (Stage 2). In the alectinib group, for both the safety-evaluation and expansion stages (Stages 1 and 2), the combination will be given to participants who are treatment-naive with anaplastic lymphoma kinase (ALK)-positive advanced NSCLC. In Stage 1, erlotinib will be given at a starting dose of 150 milligrams (mg) by mouth (PO) once daily (QD) and the starting dose of alectinib will be 600 mg twice daily (BID), for 28 consecutive days during Cycle 1 and on Days 1 through 21 of each cycle thereafter. The starting dose of atezolizumab will be 1200 mg, administered every 3 weeks (q3W) starting on Day 8 of Cycle 1. If the starting regimen for a combination treatment is not tolerated, alternative doses and/or schedules of erlotinib and atezolizumab or alectinib and atezolizumab may be tested to determine potential recommended Phase 2 dose (RP2D) for that combination treatment. In Stage 2, a potential RP2D and schedule for each combination treatment will be investigated in an expansion cohort. For both stages, continuation of treatment beyond Cycle 1 will be at the discretion of the treating investigator. Study treatment will be discontinued in participants who experience disease progression or unacceptable toxicity, are not compliant with the study protocol, or, in their opinion or in the opinion of the investigator, are not benefiting from study treatment. However, in the absence of unacceptable toxicity, participants with second-line or greater NSCLC who are still receiving atezolizumab at the time of radiographic disease progression may be permitted to continue study treatment.

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

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

A <span class="go-doc-concept go-doc-intervention">Phase 1b</span> Study of <span class="go-doc-concept go-doc-intervention">MPDL3280A</span> (an Engineered Anti-PDL1 <span class="go-doc-concept go-doc-intervention">Antibody</span>) in Combination With <span class="go-doc-concept go-doc-intervention">Tarceva</span> in Patients With Non-Small Cell <span class="go-doc-concept go-doc-disease">Lung Cancer</span>

Title

  • Brief Title: A Phase 1b Study of MPDL3280A (an Engineered Anti-PDL1 Antibody) in Combination With Tarceva in Patients With Non-Small Cell Lung Cancer
  • Official Title: A Phase 1b Study of the Safety and Pharmacology of MPDL3280A Administered With Erlotinib in Patients With Advanced Non-Small Cell Lung Cancer
  • Clinical Trial IDs

    NCT ID: NCT02013219

    ORG ID: WP29158

    Trial Conditions

    Non-Squamous Non-Small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    MPDL3280A Stage 1: Tarceva (Erlotinib) and MPDL3280A
    MPDL3280A Stage 2: Tarceva (Erlotinib) and MPDL3280A
    erlotinib [Tarceva[ Stage 2: Tarceva (Erlotinib) and MPDL3280A
    erlotinib [Tarceva] Stage 1: Tarceva (Erlotinib) and MPDL3280A

    Trial Purpose

    This open-label, multicenter study will assess the safety, tolerability, and
    pharmacokinetics of intravenous (IV) dosing of MPDL3280A and oral dosing of Tarceva
    (erlotinib) administered in combination to patients with non-small cell lung cancer (NSCLC).

    This study has two stages. In the safety evaluation stage, patients with epidermal growth
    factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-treatment-naive, advanced NSCLC will
    be given Tarceva at a starting daily dose of 150 mg for 28 consecutive days during Cycle 1
    and for 21-day cycles thereafter. The starting dose of MPDL3280A will be 1200 mg,
    administered every 3 weeks starting on Day 8 of Cycle 1. If the starting regimen is not
    tolerated, alternative doses and/or schedules of Tarceva and MPDL3280A may be tested.

    In the expansion stage, patients with previously untreated, EGFR mutation-positive, advanced
    NSCLC will be treated with a potential recommended phase 2 dose and schedule based on the
    treatment established in safety evaluation stage.

    For both stages, continuation of treatment beyond Cycle 1 will be at the discretion of the
    treating investigator. In the absence of unacceptable toxicity or disease progression,
    treatment with MPDL3280A may be continued for a maximum of 17 cycles (or 12 months,
    whichever occurs first). Tarceva may be continued until disease progression in the absence
    of unacceptable toxicity. Time on study is expected to be approximately 15 months.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Stage 1: Tarceva (Erlotinib) and MPDL3280A Experimental MPDL3280A, erlotinib [Tarceva]
    Stage 2: Tarceva (Erlotinib) and MPDL3280A Experimental MPDL3280A, erlotinib [Tarceva[

    Eligibility Criteria

    Inclusion Criteria:

    - Age >/= 18 years.

    - Histologically or cytologically documented, locally advanced or metastatic non-small
    cell lung cancer (NSCLC).

    - Patients in Stage 1 (Safety Evaluation): No limit to the number of prior therapies
    (except for EGFR TKIs).

    - Patients in Stage 2 (Expansion):

    Sensitizing mutation in the EGFR gene. Consent to collection of tumor tissue samples
    before, during, and after treatment for biopsy and PD biomarker analyses.

    - ECOG performance status of 0 or 1.

    - Life expectancy >/= 12 weeks.

    - Measurable disease, as defined by RECIST v1.1.

    - Adequate hematologic and end-organ function.

    - Use of highly effective contraception (as defined by protocol) until 6 months after
    the last dose of MPDL3280A; patients must not be pregnant or breastfeeding.

    - Tumor tissue specimen.

    Exclusion Criteria:

    - Prior treatment with any EGFR mutant-targeting TKI.

    - Patients in Stage 2 may not have received any prior treatments for their NSCLC.

    - Any approved anticancer therapy, including chemotherapy, or hormonal therapy (except
    hormone-replacement therapy or oral contraceptives) within 3 weeks of first dose.

    - Treatment with any other test drug or participation in another clinical trial within
    28 days of enrollment.

    - Known symptomatic or untreated CNS metastases. Patients with a history of treated
    asymptomatic CNS metastases may be eligible.

    - Leptomeningeal disease.

    - Uncontrolled tumor-related pain.

    - Uncontrolled pleural effusion, pericardial effusion, or ascites requiring drainage at
    least once monthly.

    - High levels of calcium requiring bisphosphonate therapy or denosumab.

    - Malignancies other than NSCLC within 5 years prior to enrollment, with the exception
    of those with a negligible risk of metastasis or death (such as adequately treated
    carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized
    prostate cancer, or ductal carcinoma in situ).

    - History of severe allergic, anaphylactic, or other reactions to chimeric or humanized
    antibodies or fusion proteins.

    - History of autoimmune disease.

    - Patients with prior bone marrow or solid organ transplantation.

    - History of lung inflammation or disease.

    - Current or active tuberculosis, hepatitis B, or hepatitis C.

    - Patients with past or resolved hepatitis B virus (HBV) infection are eligible.
    Patients positive for hepatitis C virus (HCV) antibody are eligible only if
    polymerase chain reaction (PCR) is negative for HCV RNA.

    - Signs or symptoms of infection within 2 weeks prior to first dosing.

    - Received therapeutic oral or IV antibiotics within 2 weeks prior to first dosing.

    - Significant cardiovascular disease.

    - Major surgical procedure other than for diagnosis within 28 days prior to first
    dosing or during the course of the study.

    - Administration of a live, attenuated vaccine within 4 weeks before first dosing or
    during the study.

    - Any other diseases, metabolic dysfunction, physical examination finding, or clinical
    laboratory finding that may reasonably prevent the patient from participating.

    - Any significant ophthalmologic abnormality. The use of contact lenses is not
    recommended during the study.

    - Prior treatment with CD137 agonists or immune checkpoint blockade therapies.

    - Treatment with systemic immunostimulatory agents within 6 weeks or five half-lives of
    the drug, whichever is shorter, prior to first dosing.

    - Treatment with systemic immunosuppressive medications within 2 weeks prior to first
    dosing (inhaled corticosteroids and mineralocorticoids are allowed).

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Incidence of dose-limiting toxicities

    Secondary Outcome Measures

    Incidence of adverse events

    Incidence of anti-therapeutic antibodies against MPDL3280A

    Maximum serum concentration (Cmax) of MPDL3280A

    Maximum plasma concentration (Cmax) of Tarceva

    Progression-free survival

    Overall survival

    Overall response, as determined by the investigator with RECIST v1.1

    Trial Keywords