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.
- 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.
- 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