A PHASE III, OPEN-LABEL, MULTICENTER, RANDOMIZED STUDY TO INVESTIGATE THE EFFICACY AND SAFETY OF MPDL3280A (ANTI-PD-L1 ANTIBODY) COMPARED WITH DOCETAXEL IN PATIENTS WITH NON-SMALL CELL LUNG CANCER AFTER PLATINUM FAILURE

MPDL3280A is a human immunoglobulin (Ig) G1 monoclonal antibody consisting of
two heavy chains (448 amino acids) and two light chains (214 amino acids) and
produced in Chinese hamster ovary cells. MPDL3280A was engineered to eliminate
Fc-effector function via a single amino acid substitution (asparagine to
alanine) 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 31-33

Improvement in OS is generally accepted as the best measure of clinical benefit
for
patients with advanced/unresectable or metastatic NSCLC. The assumption that
treatment with MPDL3280A will prolong OS compared with treatment with docetaxel
is
based on the durable response rates observed in Phase I trials with MPDL3280A,
as
well as other PD-L1/PD-1 blocking agents.

The secondary efficacy endpoints of PFS and ORR will allow the evaluation of
differences in response and progression patterns between the two treatment
groups. Patients will be evaluated for disease progression at predefined,
standard intervals to MPDL3280A*F. Hoffmann-La Roche Ltd.
Protocol GO28915, Version 4 58
minimize evaluation-time biases and will be followed off-treatment for
continued safety monitoring and date of death. Safety and tolerability of study
treatments will be assessed. The evaluation of efficacy data across the PD-L1
staining categories will be defined by subpopulations (TC3 or IC3, TC3 or
IC2/3, TC3 or IC1/2/3, ITT) and analyzed by a hierarchal approach to define an
appropriate diagnostic cutoff. MPDL3280A pharmacokinetics will be characterized
and exploratory biomarker analyses performed. The MPDL3280A concentration
results may be compared with available data from other MPDL3280A clinical
studies and correlated with efficacy endpoints and safety events as
appropriate. PRO data will allow further evaluation of the relative
tolerability of treatment and the impact of therapy on disease symptoms between
the two treatment groups.

Study Design

This is a Phase III, global, multicenter, open-label, randomized, controlled
study designed to evaluate the efficacy and safety of MPDL3280A compared with
docetaxel in patients with locally advanced or metastatic NSCLC who have
progressed during or following a platinum-containing
regimen.

For more detailed information, please see pages 12-14 of the study protocol.

Eligible patients will be stratified by PD-L1 IHC status (four categories of
PD-L1 expression), by the number of prior chemotherapy regimens (1 versus 2),
and by histology (nonsquamous versus squamous) and then randomized 1:1 to
receive either MPDL3280A or docetaxel.

MPDL3280A at a fixed dose of 1200 mg will be administered intravenously on Day
1 of each 21-day cycle.

Docetaxel 75 mg/m2 will be administered intravenously on Day 1 of each 21-day
cycle until disease progression per standard RECIST v1.1 or unacceptable
toxicity

For more information, see also pages 11-13 of the study protocol

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