Clarifications and additions were made to the Schedule of Activities and eligibility criteria, based on an FDA request. Clarified that crizotinib will be administered as a single agent. Clarified that participants more than or equal to (>=)21 years of age will receive crizotinib 250 mg BID, whereas participants less than (<)21 years of age will receive crizotinib 280 mg/m^2 BID.

Amended inclusion criterion #5 to allow paediatric participants with alanine aminotransaminase (ALT) and/or aspartate aminotransaminase (AST) levels less than or equal to (<=)10*the upper limit of normal and bilirubin levels <=2*the upper limit of normal to be eligible for the study. This change was made to allow access to crizotinib for those paediatric participants who are more heavily pre treated and thus, may be likely to have elevated liver function tests. Due to this change in inclusion criteria for preexisting elevations of AST and ALT, Hy’s law criteria for paediatric participants was modified accordingly. The concomitant use of drugs that elevate gastric pH including protein pump inhibitors or histamine 2 antagonists were excluded from the study. The eligibility criteria was updated to allow participants who were already receiving crizotinib (e.g. on another clinical study) and required an oral formulation. Sections 7.1.1 and 8.5: clarified that laboratory data values won’t be collected on the Case Report Form. SAEs and Grade >=3 AEs based on laboratory test abnormalities will be collected on the AE pages of the CRF. Removed screening requirement for triplicate ECGs to a single ECG measurement.

Inclusion/exclusion criteria were modified to facilitate participants’ access to crizotinib: inclusion criteria #8, #9, #10 and #11 were removed and new inclusion criterion 12 was added, to ensure recovery from prior treatment toxicities rather than a fixed time frame; exclusion criterion #3 was removed to allow inclusion of adult participants that received crizotinib before; exclusion criterion #8 was amended to exclude participants with any grade interstitial fibrosis or interstitial lung disease, not only those with grade 3-4. This change was implemented in the most recent update of the Investigator Brochure exclusion criterion #10: atazanavir was removed from the text because it is not present anymore in the FDA’s updated list of strong CYP3A inhibitors. Exclusion criterion #14 was amended to shorten the washout period, per request by site with participant in critical conditions. Section 5.3 (investigational product supplies), 5.4 (administration) and 5.9 (concomitant treatments) were updated and dosing instructions added for microsphere formulation, for consistency with revised Investigational Product manual. Appendix 2 was updated with more detailed dosing information, for oral solutions and microspheres.

Paediatric safety and anti-tumour activity data from Studies ADVL0912 and A8081013 were added (Section 1.1.3) to be consistent with the most recent update of the IB (September 2021). Prophylactic use of antiemetics for paediatric participants were added to Section 5.7.1 to be consistent with the wording in the United States Prescribing Information (USPI). To be consistent with the Dear Health Care Practitioner (DHCP) letter issued on 19 January 2021, ophthalmologic examinations were added to Table 1 (Schedule of Activities); dose modification criteria for visual events were updated in Table 2. The Protocol Administrative Change Letter (PACL) issued in April 2020 to address the impact of COVID-19 was indicated in Section 6 and included as Appendix 4.