Savolitinib vs. Sunitinib in MET-driven PRCC.

Inclusion Criteria:

1. Histologically confirmed PRCC, which is unresectable/locally advanced or metastaticwith measurable disease as per RECIST 1.1. Patients with papillary urothelialcarcinoma or renal pelvis cancer of the kidney are not considered PRCC and are noteligible.

2. Confirmation of MET-driven PRCC without co-occurring FH or VHL mutations from anFFPE tumour sample using the sponsor-designated central laboratory validated NGSassay

3. Patients who have received no prior systemic therapy as well as those who havereceived prior systemic therapy for PRCC in the advanced setting.* Patients can betreatment-naïve, or previously treated, but cannot have previously receivedsunitinib or a MET inhibitor. Patients who have received prior systemic therapy musthave had disease progression in soft tissue disease or bone within 6 months of thelast dose of the most recent systemic therapy

4. Adequate haematological, renal, cardiac and liver functions

5. Karnofsky performance status ≥ 80

Exclusion Criteria:

1. Most recent cytotoxic chemotherapy, immunotherapy, chemo-immunotherapy, orinvestigational agents <28 days from the date of randomisation. Most recent noncytotoxic targeted therapy <14 days from the date of randomisation.

2. Prior treatment with a MET inhibitor (e.g. foretinib, crizotinib, cabozantinib,onartuzumab or previous savolitinib) or sunitinb.

3. Treatment with strong inducers or inhibitors of CYP3A4 or strong inhibitors ofCYP1A2, taken within 2 weeks or not possible to be stopped for at least 2 weekbefore the date of randomisation. Herbal medications cannot be taken within 7 daysof the date of randomisation (3 weeks for St John's wort).

4. Wide field radiotherapy administered ≤28 days or limited field radiation forpalliation ≤7 days prior to the date of randomisation

5. Major surgical procedures ≤28 days of randomisation or minor surgical procedures ≤7days. No waiting is required following port-a-cath placement.

6. Previously untreated brain metastases

7. Serious active infection or gastrointestinal disease

8. Presence of other active cancers, or history of treatment for invasive cancer withinthe last 5 years.

9. Mean resting QTcF >470 msec for women and >450 msec for men on the Part 2 screeningtriplicate ECGs or factors that may increase the risk of QTcF prolongation such aschronic hypokalaemia not correctable with supplements, congenital or familial longQT syndrome, or family history of unexplained sudden death under 40 years of age infirst-degree relatives or any concomitant medication known to prolong the QTinterval and cause Torsades de Pointes