A PHASE II, MULTICENTER, SINGLE-ARM STUDY OF ATEZOLIZUMAB IN PATIENTS WITH PD L1-POSITIVE LOCALLY ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER

MPDL3280A is a human Ig G1 monoclonal antibody consisting of two heavy chains
(448 amino acids) and two light chains (214 amino acids) and is produced in
Chinese hamster ovary cells. MPDL3280A was engineered to eliminate Fc-effector
function via a single amino acid substitution at position 298 on the heavy
chain, which results in a non-glycosylated antibody that has minimal binding to
Fc receptors and prevents Fc-effector function at expected concentrations in
humans. MPDL3280A targets human PD-L1 and inhibits its interaction with its
receptors,PD-1 and B7.1 (CD80, B7-1). Both of these interactions are reported
to provide inhibitory signals to T cells.
MPDL3280A is being investigated as a potential therapy against solid tumors and
hematologic malignancies in humans.

For more information, please see also study protocol pages 53 - 64

The primary and secondary efficacy objectives analysis will be performed in
patients who are PD-L1 positive (defined as IHC 2 and IHC 3 on the basis of
tumor PD-L1 expression) and when appropriate may be performed in different
patient subpopulations according to the two IHC categories.

PRIMARY OBJECTIVE
The primary objective for this study is to evaluate the efficacy of MPDL3280A
in patients with PD-L1* positive locally advanced or metastatic NSCLC, as
measured by:
* Independent review facility (IRF)-assessed ORR according to RECIST v1.1
The efficacy analysis will follow a hierarchical fixed-sequence procedure.

SECONDARY OBJECTIVES
The secondary objectives for this study are as follows:
* To evaluate PFS and DOR, and time in response (TIR) according to RECIST v1.1
as assessed by IRF and according to modified RECIST as assessed by the
investigators
* To evaluate ORR, DOR, TIR, and PFS according to RECIST v1.1 as assessed by
the investigators
* To evaluate the investigator-assessed ORR according to modified RECIST
* To evaluate OS and 1-year OS
* To evaluate 1-year PFS as determined by the IRF per RECIST v1.1 and 1-year
PFS as determined by the investigator per RECIST v1.1 and per modified RECIST
* To evaluate the safety and tolerability of MPDL3280A
* To characterize the pharmacokinetics of MPDL3280A
* To evaluate the incidence and titers of ATAs against MPDL3280A and to explore
the potential relationship of the immunogenicity response with
pharmacokinetics, safety, and efficacy

EXPLORATORY OBJECTIVES
The exploratory objectives for this study are as follows:
* To evaluate IRF-assessed ORR according to modified RECIST
* To evaluate disease control rate (DCR)
* To evaluate tumor burden using change in sum of longest diameters (SLD)
* To evaluate the relationship between tumor biomarkers (including but not
limited to PD-L1, PD-1, and others), as defined by IHC or quantitative reverse
transcriptase*polymerase chain reaction (qRT-PCR), and/or other methods and
measures of efficacy
* To assess predictive, prognostic, and pharmacodynamic exploratory biomarkers
in archival and/or fresh tumor tissue and blood and their association with
disease status and/or response to study treatment
* To evaluate the utility of biopsy at the time of apparent disease progression
to distinguish apparent increases in tumor volume related to the
immunomodulatory activity of MPDL3280A (i.e., pseudoprogression/tumor immune
infiltration) from true disease progression
* To evaluate patient-reported outcomes (PROs) of lung cancer symptoms, patient
functioning, and health-related quality of life (HRQoL) as measured by the
European Organisation for the Research and Treatment of Cancer Quality-of-Life
Questionnaire Core 30 (EORTC QLQ-C30) and the lung cancer module (QLQ-LC13)

This is a phase II, multicenter, single-arm study to evaluate the efficacy of
MPDL3280A in patients with PD-L1*positive locally advanced or metastatic
non-small cell lung cancer.

For more detailed information, please see pages 39-49 of the study protocol.

Eligible patients will be placed in Cohort I, 2 or 3, depending on their
medical history.

MPDL3280A IV (fixed dose of 1200 mg) will be administered on Day 1 of 21-day
cycles. During the initial treatment stage, MPDL3280A treatment may be
continued as long as patients are experiencing clinical benefit as assessed by
the investigator, i.e., in the absence of unacceptable toxicity or symptomatic
deterioration attributed to disease progression after an integrated assessment
of radiographic
data, biopsy results (if available), and clinical status.
For more information, see also pages 66-68 of the study protocol.

For more information, please see the answer on question number E9.