Savolitinib Plus Durvalumab Versus Sunitinib and Durvalumab Monotherapy in MET-Driven, Unresectable and Locally Advanced or Metastatic PRCC

Papillary Renal Cell Carcinoma Clinical Trial

— SAMETA  

Official title:

A Phase III, Open Label, Randomised, 3-Arm, Multi-Centre Study of Savolitinib Plus Durvalumab Versus Sunitinib and Durvalumab Monotherapy in MET-Driven, Unresectable and Locally Advanced or Metastatic Papillary Renal Cell Carcinoma (SAMETA)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05043090
• Other study ID #: D5086C00001
• Secondary ID: 2021-000336-55
• Status: Recruiting
• Phase: Phase 3
• Start date: October 28, 2021
• Est. completion date: September 14, 2026

Study information

• Verified date: February 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A clinical trial to compare the effectiveness of savolitinib plus durvalumab versus sunitinib in MET-driven (hepatocyte growth factor receptor), unresectable and locally advanced or metastatic PRCC (Papillary Renal Cell Carcinoma).

Description:

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. Approximately 200 participants will be randomised in a 2:1:1 ratio to one of the following intervention groups: savolitinib (600mg, oral, once daily) plus durvalumab (1500mg IV Q4W), sunitinib (50mg, oral, once daily for 4 consecutive weeks, followed by a sunitinib-free interval of 2-weeks, Q6W), or durvalumab monotherapy (1500mg IV Q4W). Participants will continue to receive study intervention until objective radiological PD per RECIST 1.1 is assessed by the investigator, unacceptable toxicity occurs, consent is withdrawn or another discontinuation criterion is met. Depending on the preferred subsequent therapy, participants randomised to the durvalumab monotherapy arm will be eligible to switch to receive savolitinib in combination with durvalumab at the time of objective radiological PD assessed by BICR per RECIST 1.1, without any intervening systemic anti-cancer therapy following discontinuation of durvalumab monotherapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 220
• Est. completion date: September 14, 2026
• Est. primary completion date: May 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

• Histologically confirmed unresectable and locally advanced or metastatic PRCC
• PRCC must be centrally confirmed as MET-driven using a sponsor-designated central laboratory validated NGS assay
• No prior systemic anti-cancer treatment in the metastatic setting; no prior exposure to MET inhibitors, Durvalumab or Sunitinib in any setting
• Karnofsky Score >70
• At least one lesion, not previously irradiated, that can be accurately measured at baseline
• Adequate organ and bone marrow function
• Life expectancy =12weeks at Day 1

Exclusion Criteria:

• History of liver cirrhosis of any origin and clinical stage; or history of other serious liver disease or chronic disease with relevant liver involvement, with or without normal LFTs
• Spinal cord compression or brain metastases, unless asymptomatic and stable on treatment for at least 14 days prior to study intervention
• Active or prior cardiac disease (within past 6 months) or clinically significant ECG abnormalities and/or factors/medications that may affect QT and/or QTc intervals
• Active infection including HIV, TB, HBV and HCV
• Active or prior documented autoimmune or inflammatory disorders
• Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Papillary Renal Cell Carcinoma

Intervention

Drug:
• savolitinib
Tablets : 3 × 200 mg tablets once daily
• durvalumab
Concentrate for solution for IV infusion : 1500 mg durvalumab every 4 weeks
• sunitinib
Capsules : 2 x 25mg capsules once daily 4 weeks on, 2 weeks off

Locations

Country	Name	City	State
Argentina	Research Site	Bahía Blanca
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Caba
Argentina	Research Site	Ciudad Autónoma Buenos Aires
Argentina	Research Site	Cordoba
Argentina	Research Site	La Plata
Argentina	Research Site	Rosario
Argentina	Research Site	San Miguel de Tucuman
Australia	Research Site	Box Hill
Australia	Research Site	Macquarie University
Australia	Research Site	Malvern
Australia	Research Site	St Leonards
Brazil	Research Site	Belo Horizonte
Brazil	Research Site	Brasilia
Brazil	Research Site	Cachoeiro De Itapemirim
Brazil	Research Site	Criciuma
Brazil	Research Site	Curitiba
Brazil	Research Site	Florianopolis
Brazil	Research Site	Fortaleza
Brazil	Research Site	Natal
Brazil	Research Site	Pelotas
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Salvador
Brazil	Research Site	São Jose do Rio Preto
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Vitoria
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Montreal	Quebec
Chile	Research Site	Providencia
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Temuco
China	Research Site	Beijing
China	Research Site	Changsha
China	Research Site	Changsha
China	Research Site	Chengdu
China	Research Site	Chongqing
China	Research Site	Harbin
China	Research Site	Jinan
China	Research Site	Nanchang
China	Research Site	Nanjing
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Tianjin
China	Research Site	Xi'an
China	Research Site	Zhengzhou
Czechia	Research Site	Brno
Czechia	Research Site	Hradec Kralove
Czechia	Research Site	Olomouc
Czechia	Research Site	Praha
Czechia	Research Site	Praha 10
Czechia	Research Site	Praha 5
Czechia	Research Site	Praha 8
France	Research Site	Bordeaux
France	Research Site	Nice
France	Research Site	Toulouse Cedex 9
France	Research Site	Villejuif
Germany	Research Site	Hamburg
Germany	Research Site	Hannover
Germany	Research Site	München
Germany	Research Site	Tübingen
Germany	Research Site	Ulm
Hong Kong	Research Site	Hong Kong
Hong Kong	Research Site	Shatin
India	Research Site	Bangalore
India	Research Site	Belagavi
India	Research Site	Jaipur
India	Research Site	Kochi
India	Research Site	Kolkata
India	Research Site	Mumbai
India	Research Site	Mysore
India	Research Site	Nashik
India	Research Site	Nashik
Israel	Research Site	Ashdod
Israel	Research Site	Haifa
Israel	Research Site	Jerusalem
Israel	Research Site	Jerusalem
Israel	Research Site	Petah Tikva
Israel	Research Site	Rehovot
Israel	Research Site	Safed
Israel	Research Site	Tel-Aviv
Italy	Research Site	Arezzo
Italy	Research Site	Avellino
Italy	Research Site	Bari
Italy	Research Site	Bologna
Italy	Research Site	Firenze
Italy	Research Site	Meldola
Italy	Research Site	Milan
Italy	Research Site	Milano
Italy	Research Site	Napoli
Italy	Research Site	Padova
Italy	Research Site	Reggio Emilia
Italy	Research Site	Tricase
Italy	Research Site	Verona
Korea, Republic of	Research Site	Daejeon
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Incheon
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Mexico	Research Site	Aguascalientes
Mexico	Research Site	Cancún
Mexico	Research Site	México
Mexico	Research Site	Monterrey
Mexico	Research Site	Queretaro
Mexico	Research Site	Toluca De Lerdo
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Arnhem
Netherlands	Research Site	Rotterdam
Poland	Research Site	Gdansk
Poland	Research Site	Gdynia
Poland	Research Site	Kraków
Poland	Research Site	Otwock
Poland	Research Site	Poznan
Poland	Research Site	Poznan
Poland	Research Site	Warsaw
Romania	Research Site	Baia Mare
Romania	Research Site	Cluj Napoca
Romania	Research Site	Cluj-Napoca
Romania	Research Site	Constanta
Romania	Research Site	Craiova
Romania	Research Site	Craiova
Romania	Research Site	Iasi
Russian Federation	Research Site	Arkhangelsk
Russian Federation	Research Site	Ekaterinburg
Russian Federation	Research Site	Krasnoyarsk
Russian Federation	Research Site	Kursk
Russian Federation	Research Site	Kuzmolovskiy
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Omsk
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	St-Petersburg
Singapore	Research Site	Singapore
Slovakia	Research Site	Trencin
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Cordoba
Spain	Research Site	Coruña
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Majadahonda
Spain	Research Site	Málaga
Spain	Research Site	Pamplona
Spain	Research Site	Sabadell
Spain	Research Site	Sevilla
Spain	Research Site	Valencia
Taiwan	Research Site	Kaohsiung City
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan
Turkey	Research Site	Adana
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Edirne
Turkey	Research Site	Istanbul
Turkey	Research Site	Istanbul
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
Turkey	Research Site	Karsiyaka
Turkey	Research Site	Kazimkarabekir
Ukraine	Research Site	Chernivts?
Ukraine	Research Site	Dnipropetrovsk
Ukraine	Research Site	Ivano-Frankivsk
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Poltava
Ukraine	Research Site	Zaporizhzhia
Ukraine	Research Site	Zaporizhzhia
United Kingdom	Research Site	Leicester
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United States	Research Site	Boston	Massachusetts
United States	Research Site	Columbia	Maryland
United States	Research Site	Gurnee	Illinois
United States	Research Site	New York	New York
United States	Research Site	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Canada,  Chile,  China,  Czechia,  France,  Germany,  Hong Kong,  India,  Israel,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Romania,  Russian Federation,  Singapore,  Slovakia,  Spain,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS) /savolitinib plus durvalumab relative to sunitinib	Defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.; The analysis will include all randomised participants as randomised, regardless of whether the participant withdraws from therapy, receives another anti-cancer therapy or clinically progresses prior to RECIST 1.1 progression.	Approximately 28 months post first subject randomized
Secondary	Overall Survival (OS) /savolitinib plus durvalumab relative to sunitinib	Defined as time from randomisation until the date of death due to any cause. The comparison will include all randomised participants as randomised regardless of whether the participant withdraws from therapy or receives another anti-cancer therapy.	Approximately 28 months and approximately 42 months post first subject randomized
Secondary	Objective Response Rate (ORR) / savolitinib plus durvalumab relative to sunitinib	Defined as the proportion of participants who have a Complete Response (CR) or Partial Response (PR) as determined by BICR per RECIST 1.1.	Approximately 28 months post first subject randomized
Secondary	Duration of Response (DoR) / savolitinib plus durvalumab relative to sunitinib	Defined as the time from the date of first documented response until date of documented progression per RECIST 1.1 as assessed by BICR or death due to any cause.	Approximately 28 months post first subject randomized
Secondary	Disease Control Rate (DCR) at 24 and 48 weeks /savolitinib plus durvalumab relative to sunitinib	Defined as the percentage of participants who have a CR or PR or who have Stable Disease (SD) per RECIST 1.1 as assessed by BICR for at least 23 or 47 weeks, respectively after randomisation.	Approximately 28 months post first subject randomized
Secondary	Time from randomisation to second progression or death (PFS2) /savolitinib plus durvalumab relative to sunitinib	Defined as time from randomisation to the earliest of the progression event (following the initial progression), subsequent to the first subsequent therapy or death.	Approximately 28 months and 42 months post first subject randomized
Secondary	Assessment of patient-reported symptoms, functioning, and HRQoL /savolitinib plus durvalumab relative to sunitinib	Time to deterioration and change from baseline in symptoms, functioning, and HRQoL as measured by FKSI-19.	Approximately 28 months post first subject randomized
Secondary	Objective Response Rate (ORR) / savolitinib plus durvalumab relative to durvalumab monotherapy	Defined as the proportion of participants who have a Complete Response (CR) or Partial Response (PR) as determined by BICR per RECIST 1.1	Approximately 28 months post first subject randomized
Secondary	Duration of Response (DoR) / savolitinib plus durvalumab relative to durvalumab monotherapy	Defined as the time from the date of first documented response until date of documented progression per RECIST 1.1 as assessed by BICR or death due to any cause.	Approximately 28 months post first subject randomized
Secondary	Progression-Free Survival (PFS) /savolitinib plus durvalumab relative to durvalumab monotherapy	Defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.; The analysis will include all randomised participants as randomised, regardless of whether the participant withdraws from therapy, receives another anti-cancer therapy or clinically progresses prior to RECIST 1.1 progression.	Approximately 28 months post first subject randomized
Secondary	Evaluation of the PK of savolitinib pre-dose	Plasma concentration of savolitinib and its metabolites pre-dose (Ctrough / trough plasma concentration : measured concentration at the end of a dosing interval at steady state [taken directly before next administration]) in participants randomised to savolitinib plus durvalumab.	Approximately 28 months post first subject randomized
Secondary	Evaluation of the PK of savolitinib post-dose	Plasma concentration of savolitinib and its metabolites post-dose (C1h and C3h) in participants randomised to savolitinib plus durvalumab.	Approximately 28 months post first subject randomized
Secondary	Evaluation of the PK of durvalumab pre-dose	Serum concentration of durvalumab pre-dose (Ctrough / trough plasma concentration : measured concentration at the end of a dosing interval at steady state [taken directly before next administration]) in participants randomised to savolitinib plus durvalumab or durvalumab monotherapy.	Approximately 28 months post first subject randomized
Secondary	Evaluation of the PK of durvalumab / Cmax (maximum plasma concentration)	Serum concentration of durvalumab at the end of infusion (Cmax) in participants randomised to savolitinib plus durvalumab or durvalumab monotherapy.	Approximately 28 months post first subject randomized