1.The following text was added to Dose Escalation and Extension Phases for the Smaller Subject Cohort (Subjects Weighing <45 kg) "If the MTD can be determined for subjects weighing <45 kg, then these subjects may be enrolled in the extension phase at the recommended dose. If the MTD is the same for subjects weighing <45 kg as for those weighing >=45 kg, then subjects weighing <45 kg and enrolled in the extension phase will count as part of the 20 subjects required for extension phase accrual and analysis.” 2.The squamous cell carcinoma (SCC) risk management plan to monitor for the occurrence of new primary melanoma and both cutaneous and non-cutaneous SCCs was updated. The appropriate sections of the protocol were revised to reflect this change. 3.The text was revised to state that an electrocardiogram (ECG) was required at the treatment completion visit. This had been inadvertently omitted in the original protocol and was changed to align with the Paediatric Investigation Plan (PIP). 4.The text was revised to state that tissue samples of any new primary melanoma or SCC (cutaneous and non cutaneous) were to be submitted to a central pathology laboratory to undergo molecular characterization. 5.The definitions of adverse event of special interest (AESIs) were revised to align with the vemurafenib program. The list of AESIs was changed to: a) Grade >=3 phototoxicity b) Grade >=3 QTc prolongation c) Grade >=4 elevations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin d) SCC (cutaneous and non-cutaneous including keratoacanthoma [KA]) e) New primary melanoma f) Non-SCC/KA suspicious skin lesions 6.Definition of Women of Childbearing Potential and Acceptable and Unacceptable Forms of Contraception was revised to shorten from 12 months to 6 months the period that women of childbearing potential were required to use 2 forms of acceptable contraception following discontinuation of vemurafenib.

1.The definitions of AESIs were revised as follows: a) ”A new primary invasive malignancy (other than cuSCC or new primary melanoma) or progression or recurrence of a prior invasive malignancy (other than the disease under study)” was added. b) ”Grade >=3 phototoxicity” was deleted. c) ”Non-SCC/KA suspicious skin lesions” was deleted. 2.Additional Assessments for SCC risk management plan [Treating Physician]) was clarified that chest CT scans that were required following study drug discontinuation needed to be obtained only up to 6 months after study drug discontinuation.

1.The purpose of the amendment was to update the safety information in the Introduction section of the protocol, and to make other minor changes to improve clarity and consistency.