A Phase III, Open Label, Randomised, 3 Arm, Multi Centre Study of Savolitinib plus Durvalumab versus Sunitinib and Durvalumab Monotherapy in Participants with MET Driven, Unresectable and Locally Advanced or Metastatic Papillary Renal Cell Carcinoma (PRCC)

Papillary RCC is the most common subtype of nccRCC, accounting for 10% to 15%
of renal malignancies. Few studies have evaluated a specific treatment for PRCC
as the primary histologic tumour type. In practice, treatment of PRCC is based
on data from studies conducted in ccRCC, and international clinical guidelines
recommend a clinical study as one of the preferred options for treatment of
advanced/metastatic PRCC patients. Therefore, effective treatment for patients
with PRCC represents an unmet medical need. Abnormalities of MET are not only a
differentiating characteristic of PRCC, but may be a potential therapeutic
target. The MET pathway may also be involved in immunomodulation. Non-clinical
and clinical data suggest that there is a potential synergistic anti-tumour
effect of a MET inhibitor in combination with an immune checkpoint inhibitor.
The SAMETA study aims to evaluate the efficacy and safety of the savolitinib
plus durvalumab combination compared with sunitinib in first-line participants
with unresectable and locally advanced or metastatic PRCC that is MET driven
without co-occurring FH mutations. The study will also investigate the
contribution of durvalumab to the savolitinib plus durvalumab combination.

This study has been transitioned to CTIS with ID 2022-503105-38-00 check the CTIS register for the current data.

The purpose of this study is to assess whether a new combination treatment
(Savolitinib and Durvalumab) is better than standard treatment sunitinib in
MET-driven PRCC. The study will also assess the contribution of one part of the
combination (Durvalumab) into the overall treatment efficacy.

This is a Phase III, randomised, open label, 3 arm, multi-centre, international
study assessing the efficacy and safety of savolitinib plus durvalumab compared
with sunitinib in participants with MET-driven (without co-occurring FH
mutations), unresectable and locally advanced or metastatic PRCC, who have not
received any prior systemic anti-cancer therapy in the metastatic setting. The
study will also investigate the contribution of durvalumab to the savolitinib
plus durvalumab combination.

See also protocol v1.0. - par 1.2, figure 1 Study Design

The treatments options include
1) treatment with 2 investigational drugs, savolitinib and durvalumab in
combination;
2) treatment with 1 investigational drug, durvalumab, alone; and
3) treatment with sunitinib which is a standard treatment for PRCC.

See also protocol v1.0 par 6. Study Intervention

Overall the benefit/risk assessment supports the further investigation of
savolitinib plus durvalumab versus sunitinib in participants with MET-driven,
unresectable and locally advanced or metastatic PRCC based upon: the
non*clinical and clinical safety profile of savolitinib and durvalumab as
monotherapies, the preliminary clinical safety profile of savolitinib in
combination with durvalumab from the CALYPSO study, the risk minimisation
and AE management plans, the study design, the limited life expectancy due to
malignant disease, the lack of effective alternative treatments, the strength
of the scientific hypothesis under evaluation based on efficacy data of
savolitinib monotherapy from Phase II and III studies (SAVOIR) in PRCC, the
anti-tumour activities of other IO monotherapies in PRCC, non-clinical data
showing potential synergistic anti-tumour activities of MET inhibition and
anti-PD-L1, and emerging clinical efficacy signals from CALYPSO study.

See protocol v1.0 par 2.3.3