Savolitinib vs. Sunitinib in MET-driven PRCC

Inclusion Criteria:

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

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

3. Patients who have received no prior systemic therapy as well as those who have
received prior systemic therapy for PRCC in the advanced setting.* Patients can be
treatment-naïve, or previously treated, but cannot have previously received sunitinib
or a MET inhibitor. Patients who have received prior systemic therapy must have had
disease progression in soft tissue disease or bone within 6 months of the last 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, or
investigational agents <28 days from the date of randomisation. Most recent non
cytotoxic 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 of CYP1A2,
taken within 2 weeks or not possible to be stopped for at least 2 week before the date
of randomisation. Herbal medications cannot be taken within 7 days of the date of
randomisation (3 weeks for St John's wort).

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

5. Major surgical procedures ≤28 days of randomisation or minor surgical procedures ≤7
days. 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 within
the last 5 years.

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