The following changes were made: • Revised dates for first and last participant enrolled • Removed the requirement for neuropilin-1 (NRP-1) sampling • The relationship between tivozanib and sorafenib drug levels and activity and tivozanib and sorafenib drug levels and adverse events (AEs) were added as tertiary objectives • Revised start of treatment from within 10 days to within 14 days after randomisation • Clarified classification of prior treatment for the purpose of stratification: “In the event a participant had both 2 TKIs and a checkpoint inhibitor, the participant will be stratified according to the most recent line of therapy.” • Revised inclusion criteria (IC) and exclusion criteria (EC): o IC - removed “mixed tumor containing predominantly sarcomatoid cells” o EC – clarified eligibility of patients with CNS metastasis; removed “Participants are not considered to have a currently active malignancy if they have completed anti-cancer therapy and have been disease free for >2 years”. o EC – allowed for creatinine clearance to be calculated or measured o EC – clarified uncontrolled hypertension, removed “documented on 2 consecutive measurements taken at least 24 hours apart.” • Increased the duration of contraceptive use after the last dose of study drug for females • Tests for bicarbonate and total triiodothyronine (T3) are optional • Clarified timing of study drug shipment to the site • Clarified determination of PFS using RECIST 1.1 • Clarified dose modification for drug-related AEs • Provided further detail on the safety monitoring committee (SMC) • Updated Appendix (RECIST 1.1) to require brain scans at screening • Updated Appendix (Cytochrome P450 [CYP3A4] Inhibitors and Inducers) to include only strong inducers or inhibitors of CYP3A4 • Updated Appendix (Sorafenib Prescribing Information) • Interactive voice response system was deleted • Clarified treatment stratification

The primary data analysis was based on a data cut-off on 04 Oct 2018 with a targeted number of 242 PFS events.