• To specifically state in inclusion criterion #2 (IC #2) that patients with histologically or cytologically proven diagnosis of unresectable B3 thymoma or thymic carcinoma, as per the World Health Organization (WHO) classification of tumours of the thymus, can be included in the study. • To specify the time window in days for performing the oncologic assessment at 3 months, i.e. between days 92 and 98 after first drug administration. • To add the possibility to investigate the baseline status of additional biomarkers related to the mechanism of action for the compound PHA-848125AC in tumor biopsies. • To delete the reference to an expert pathologist reviewing the tumor tissue slides used for biomarkers analyses. • To notify changes in Sponsor Study Management Personnel and Sponsor Additional Trial Personnel.

• To change IC No. 10, by adding calculated creatinine clearance (CrCl) as a parameter to evaluate patients' renal function at study entry; • To add the recommendation to monitor patients for events indicative of, or suggestive of, TMA/HUS (Thrombotic Microangiopathy/Hemolytic Uremic Syndrome) and in case of such events to temporarily hold study drug administration and to perform specific analyses to determine whether the events are compatible with TMA/HUS. • To add information related to a new IMP (Investigational Medicinal Product) packaging and labeling.

• To reduce the frequency of visits at the site for patients who had already received 6 treatment cycles and remain on treatment for a longer period of time (more than 6 cycles). • To reconsider study protocol indications on time points of oncological assessment at 3 months, as per protocol required between 92 to 98 days from first drug administration. In some instances, this requirement cannot be fulfilled by centers because of technical and logistical reasons thus causing oncologic assessment to be made beyond the 98th day. For the purpose of the analysis, the assessments performed before the next scheduled one, i.e. on day 135 (42 days after the 3rd month assessment) in the evaluation of the main endpoint was to be accounted with the outcome they had, regardless of the timing of measurement. • To better clarify the definition of “patients evaluable for efficacy analysis” since it was misleading in the study protocol. • To update the shelf life of the 50 mg and 100 mg capsules and to delete the 10 mg capsules since not used in the current study.

• To notify study discontinuation. Enrollment was completed on April 2016 and since sufficient data were already collected and the primary efficacy endpoint of the study was already achieved (i.e., the progression free survival status at 3 months was obtained in 24 out of the 52 evaluable patients (46.2%) i.e., more than the 14 successes required by protocol), a data cut-off on 31 May 2017 was planned, in order to proceed with clinical database closure and the preparation of the Clinical Study Report. The Sponsor continued to guarantee the supply of the investigational compound until the patients still on treatment would have benefit from the therapy. After the cut-off date, all the assessments data pertaining to the patients still on treatment were no longer collected in the Case Report Form, but only in the patient’s medical notes. Safety was to be followed up for Serious Adverse Events only: SAEs were to be notified to CLIOSS Pharmacovigilance up to 28 days after the last patient had taken his/her milciclib maleate last dose. The intention with this data cut-off of 31 May 2017 was to bring the study schedule more closely aligned to standard clinical practice. • End of study definition. End of study can only occur when the last patient had discontinued study therapy, and a follow up period would have no longer performed. • Administrative changes: Tiziana Life Sciences PLC entered as new Sponsor for CDKO-125a-006 trial. With this amendment the name of Nerviano Medical Sciences (NMS) has been replaced with Tiziana Life Sciences, PLC (Tiziana) throughout the whole documents.