Local Amendment Germany In the current protocol, the pelvic CT scan is asked to be performed at Baseline for tumour assessment among others. However in Germany, pelvic CT scan will lead to an over-exposure of radiation as defined by the Bundesamt für Strahlenschutz. To fulfil this requirement, the pelvic CT scan / MRI will be optional. Moreover, the sponsor’s personnel list is updated.

PM 0259 CA 232 J1 is a prospective study which aims to assess an alternative schedule of treatment with oral vinorelbine for a category of advanced NSCLC (non-small cell lung cancer) whose medical conditions makes the use of intensive doublet not suitable. This study compares the use of oral vinorelbine as single agent in first-line treatment using a fractionated administration (metronomic) approach versus the approved dosing scheme of oral vinorelbine in patients considered as unfit for a platinum-based regimen. As planned per protocol, an interim analysis of safety was performed after the first 40 patients (20 in each arm) enrolled. All safety data were reviewed by the Data Monitoring Committee (DMC). Further to this review the DMC has issued the following recommendations regarding the conduct of the trial: To implement in both arms standard practice for infection prevention in these high-risk patients unfit for platinum-based chemotherapy, as the study protocol is addressed to patients more likely to have comorbidities that significantly expose them to infection.; To perform a second interim analysis of safety when accrual of 40 additional patients would have been reached (in total 80 patients enrolled, 40 patients in each arm). Furthermore several additional changes were implemented: -An harmonization of the definition of febrile neutropenia in accordance with NCI-CTC v.4 in use in this trial; -A clarification of the definition of “ G4PFS” (progression-free survival without Grade 4 Toxicity), of “ G2PFS” (progression-free survival without Grade 2 Toxicity); addition of definition of progression-free survival (PFS); -An update of the list of Sponsor’s representatives.

As of today, 167 patients have been randomized in the study, two patients (1 patient in Greece & 1 patient in Poland), both randomized in metronomic arm, are still receiving study medication and 27 other patients are still alive in Follow-up period. The final analysis requires the confirmation of at least 143 events (Grade 4 toxicity, Disease Progression or Death) and 162 events have been documented so far in the study. The statistical power needed to perform the final analysis of the study primary endpoint and the maturity of data of the secondary endpoints have been achieved. Therefore, to proceed with the final analysis earlier as planned per protocol, this amendment aims to modify the end of study definition as follows: The end of study is defined as: 30 days following the last study drug administration of the last patient. No additional information will be collected from 30 days following the last study drug administration. A data cut-off date for final analysis is fixed on 15-Oct-2018. Statistical analysis will contain all data generated up to 15-Oct-2018 inclusive or the end of study, whichever occurs first. • For patients having discontinued the study at the data cut-off date (15-Oct-2018), only data generated up to 15-Oct-2018 inclusive will be collected into e-CRF and analysed. • Patients who remain on study treatment at the data cut-off date (15-Oct-2018) may continue to benefit receiving treatment in the study until documented progressive disease, unacceptable toxicity, patient’s refusal, or investigator’s discretion for subject’s interest as defined in the study protocol. Study procedures during treatment period will remain unchanged except the completion of the Quality of Life questionnaire (EORTC QLQ C30) which will not be longer required to decrease the burden of patients in the study. Pierre Fabre Medicament will supply study drug, free of charge to each centre. The efficacy and safety reporting will be maintained as per protocol