A Phase IIIb/IV Safety Trial of Flat Dose Nivolumab in Combination with Ipilimumab in Participants with Non-Small Cell Lung Cancer

This is a clinical trial of nivolumab combined with ipilimumab in patients,
with newly diagnosed stage IV or recurrent non-small cell lung cancer (NSCLC),
who have not received prior systemic anticancer therapy (1st Line NSCLC), or
with stage IIIB, or with recurrent or progressive disease following multimodal
therapy (2nd line NSCLC), or in a special patient population (NSCLC patients
with renal or hepatic dysfunction, with a controlled HIV infection, with
asymptomatic brain metastases, or with a ECOG PS 2).
Lung cancer is the leading cause of cancer and cancer-related deaths globally,
accounting for 1.8 million new cases and 1.6 million deaths worldwide in 2012.
A significant number of patients have advanced lung cancer at diagnosis.
Unfortunately with current standard of care chemotherapy, the survival rate
remains poor, with less than 5% of advanced lung cancer patients alive five
years on from diagnosis.
There is a clear unmet medical need for patients with advanced NSCLC.
Nivolumab, is a new type of immunotherapy drug which stimulates the body*s own
immune system to help attack cancer cells. It works by blocking a protein on
the body*s immune cells, called PD1, so that tumours can be recognised as
foreign and attacked by the immune system. Ipilimumab is already on the market
for the treatment of melanoma.
Following a screening period, eligible patients will receive treatment with
flat dose nivolumab combined with weight-based ipilimumab. Patients will
receive study drugs until their cancer progresses or their doctor decides they
should come out of the study.
Patients will undergo the following procedures during the study: tumour tissue
biopsy (if no tumor tissue available at screening), CT/MRI scans, physical
exams, vital signs and blood sampling for routine safety testing and study
specific testing. 1000 patients will be treated in the study with approximately
22 being treated in the Netherlands.

To establish the efficacy and safety of nivolumab administered as a flat dose
in combination with weight-based ipilimumab dosing.

This is a single-arm, open-label study of nivolumab and ipilimumab in patients
with newly diagnosed histologically confirmed metastatic or recurrent non small
cell lung cancer (NSCLC). Subjects will receive treatment with nivolumab 240 mg
as a 30 minute infusion every 2 weeks and ipilimumab 1 mg/kg as a 30 minute
infusion every 6 weeks, until progression, unacceptable toxicity, withdrawal of
consent, or the study ends, whichever occurs first. After treatment, all
subjects will enter the follow-up phase of the study. Subjects will have 2
visits within the first 4 months after stopping treatment. The remaining
follow-up visits can be conducted over the phone and will occur every 3 months.
Follow up data will be collected for up to 5 years. Subjects who are determined
to be benefitting from study treatment after analysis of the primary endpoint
is completed may be eligible to continue receiving study drug.

Subjects will receive open-label treatment with nivolumab (flat dose of 240 mg
every two weeks) in combination with ipilimumab (1 mg/kg every 6 weeks). Both
nivolumab and ipilimumab are provided by the sponsor.

As part of the trial, patients will be expected to attend multiple clinic
visits, where they will undergo physical examinations, vital sign measurements,
blood tests for safety assessment, pregnancy testing (for females of child
bearing potential), and monitoring for adverse events. In addition, every 6
weeks (from week 6 until week 48) and then every 12 weeks, patients will
undergo radiographic assessment of their tumors (by CT or MRI) until disease
progression or treatment discontinuation whichever occurs later. Blood will
also be collected at certain visits for research purposes (PK, immunogenicity
and biomarker studies). The frequency of visits and number of procedures
carried out during this trial would typically be considered over and above
standard of care. These procedures are conducted by medically trained
professionals and every effort will be made to minimise any risks or discomfort
to the patient.