OPEN-LABEL PHASE Ib/II, MULTICENTER STUDY OF THE COMBINATION OF RO5479599 WITH CARBOPLATIN AND PACLITAXEL IN PATIENTS WITH ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) OF SQUAMOUS HISTOLOGY WHO HAVE NOT RECEIVED PRIOR CHEMOTHERAPY OR TARGETED THERAPY FOR NSCLC

This is a scientific study of RO5479599, an agent that binds to the HER3
receptor of malignant tumors, resulting in tumor cell apoptosis. Preclinical
research has demonstrated antitumor effect of RO5479599; a greater anti-tumor
effect was seen when the drug was used in combination with anti-EGFR therapy.
This study of RO5479599 aims to gain insight into the action of the drug in
combination with carboplatin and paclitaxel in patients with advanced or
metastatic non-small cell lung cancer (NSCLC) of squamous histology.

RO5479599 is an experimental drug under investigation by F. Hoffmann-La Roche
for the treatment of solid tumors with a HER3 over-expressed, in this study
focused on patients with advanced / metastatic non-small cell lung cancer
(NSCLC) of squamous cell histology.

This is an open-label, multicenter, single-arm Phase Ib / II study of the
combination of RO5479599 with Carboplatin and Paclitaxel in patients with
advanced / metastatic non-small cell lung cancer (NSCLC) of squamous histology,
who have not received prior chemotherapy or targeted therapy for NSCLC. The
study consists of a Safety Run-In Phase followed by an Efficacy Phase. The
study begins with a Safety Run-In Phase with a minimum of 10 and up to 20
evaluable patients. Patients will be treated with a fixed dose of 800 mg
RO5479599, administered according to a Q3W schedule, plus Carboplatin and
Paclitaxel as a standard of care. Patients will be observed for 6 weeks (i.e.
during two treatment cycles bloedvalues and vital signs will be measured at
certain timepoints, please refer to the schedual of assessments in the protocol
for further information) in order to confirm the dose and schedule that will be
used in the Efficacy Phase of the study. To demonstrate efficacy of the product
about 33 patients will be observed in the Efficacy Phase of the study.

Patients eligible for participation in this study are treated with RO5479599
and Carboplatin or Paclitaxel according to the study specific schedule as
described on page 55/56 of the Protocol.

Until now there have been no major safety issues reported in patients who have
received RO5479599. Animal studies previously performed also do not indicate
adverse events associated with RO5479599. Animals showed inflammatory reactions
against RO5479599. Based on preliminary results, such a reaction in humans is
rare. Mainly during the first injection (and up to 24 hours) there is a risk
of an Infusion Related Reaction (IRR) or an allergic reaction. The most common
adverse events in clinical studies already carried out with RO5479599 are
diarrhea, fatigue, loss of appetite, rash or dry skin, mucosal inflammation and
IRRs.
The test procedures and treatments may entail risks and cause discomfort. There
is a slight chance of pain or a bruise when blood is collected. Some people may
faint when blood is collected. During this study, with patient approval,
biopsies may be performed. The following risks are associated with a biopsy:
bruising, bleeding, infection and side-effects of the numbing medication
(anaesthetic) that may be given for the procedure. In rare cases, these risks
may be life-threatening and make hospitalization necessary. In order to reduce
the risks, the site of the biopsy will be numbed and sterile techniques will
be used.
Undergoing an MRI or PET / CT scan may entail additional discomfort,
specifically, a sense of claustrophobia (being *locked in*) or suffering from
the noise during the scan.
The disadvantages of participating in this study are: time investment to
undergo various procedures for this study, additional or prolonged
hospitalization(s), additional blood collection, additional examinations,
biopsies and any side effects of RO5479599.

An allergic reaction to the study medication may be mild (skin rash, fever,
chills, headache, nausea or vomiting) or severe (low blood pressure, elevated
heart rate, anxiety and / or difficulty swallowing or breathing). These
side-effects are most common during the first few doses, but may occur during
any infusion. The research physician may prescribe medication and other
supportive care in order to reduce or prevent the severity of these
side-effects. In rare cases, these symptoms can be so severe that they possibly
require the administration of RO5479599 to be stopped permanently.
Sometimes, side-effects develop and get worse over time due to the development
of antibodies against the study medication. Usually these side-effects involve
skin rashes, joint and muscle pain, fever and fatigue. Medication may be
prescribed to reduce the effect of these symptoms. If these side-effects are
serious or persist for a very long time, it may be necessary to permanently
stop administration of RO5479599.
Studies with laboratory animals have not shown RO5479599 to affect
cardiovascular tissue. Patients will be monitored closely during the study. For
example, multiple electrocardiograms (ECGs) will be made.
Risk of drug interactions:
It is possible that treatment with RO5479599 may affect the activity of other
medication.
Patient may experience one or more of these side-effects, or currently unknown
side effects, and they may be mild, moderate, severe, or (in very rare cases)
life-threatening or even fatal. If side-effects do occur, the study physician
must be notified immediately. He / she may prescribe medication to combat any
discomfort. Furthermore, in the event of a serious reaction, the study
physician may decide to suspend or permanently terminate treatment with the
study medication.