Clinical trial NCT05043090: Savolitinib Plus Durvalumab Versus Sunitinib and Durvalumab Monotherapy in MET-Driven, Unresectable and Locally Advanced or Metastatic PRCC
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Papillary Renal Cell Carcinoma
Keywords: Locally
Advanced
Metastatic
Carcinoma
Savolitinib
Sunitinib
Durvalumab
MET Driven
Papillary Renal Cell Carcinoma
Renal Cell
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2021-09-13
Enrollment: 148
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed 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objective radiological PD per RECIST 1.1 is assessed by the investigator, unacceptable toxicity occurs, consent is withdrawn or another discontinuation criterion is met.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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-Free Survival (PFS) /savolitinib plus durvalumab relative to sunitinib
timeFrame: Approximately 28 months post first subject randomized
Secondary outcomes:
measure: Overall Survival (OS) /savolitinib plus durvalumab relative to sunitinib
timeFrame: Approximately 28 months and approximately 42 months post first subject randomized
measure: Objective Response Rate (ORR) / savolitinib plus durvalumab relative to sunitinib
timeFrame: Approximately 28 months post first subject randomized
measure: Duration of Response (DoR) / savolitinib plus durvalumab relative to sunitinib
timeFrame: Approximately 28 months post first subject randomized
measure: Disease Control Rate (DCR) at 24 and 48 weeks /savolitinib plus durvalumab relative to sunitinib
timeFrame: Approximately 28 months post first subject randomized
measure: Time from randomisation to second progression or death (PFS2) /savolitinib plus durvalumab relative to sunitinib
timeFrame: Approximately 28 months and 42 months post first subject randomized
measure: Assessment of patient-reported symptoms, functioning, and HRQoL /savolitinib plus durvalumab relative to sunitinib
timeFrame: Approximately 28 months post first subject randomized
measure: Objective Response Rate (ORR) / savolitinib plus durvalumab relative to durvalumab monotherapy
timeFrame: Approximately 28 months post first subject randomized
measure: Duration of Response (DoR) / savolitinib plus durvalumab relative to durvalumab monotherapy
timeFrame: Approximately 28 months post first subject randomized
measure: Progression-Free Survival (PFS) /savolitinib plus durvalumab relative to durvalumab monotherapy
timeFrame: Approximately 28 months post first subject randomized
measure: Evaluation of the PK of savolitinib pre-dose
timeFrame: Approximately 28 months post first subject randomized
measure: Evaluation of the PK of savolitinib post-dose
timeFrame: Approximately 28 months post first subject randomized
measure: Evaluation of the PK of durvalumab pre-dose
timeFrame: Approximately 28 months post first subject randomized
measure: Evaluation of the PK of durvalumab / Cmax (maximum plasma concentration)
timeFrame: Approximately 28 months post first subject randomized
Other outcomes:
Locations:
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: New York
country: United States
facility: Research Site
state: New York
city: Buenos Aires
country: Argentina
facility: Research Site
city: Caba
country: Argentina
facility: Research Site
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Research Site
city: Ciudad Autónoma Buenos Aires
country: Argentina
facility: Research Site
city: Cordoba
country: Argentina
facility: Research Site
city: La Plata
country: Argentina
facility: Research Site
city: Rosario
country: Argentina
facility: Research Site
city: San Miguel de Tucuman
country: Argentina
facility: Research Site
city: Box Hill
country: Australia
facility: Research Site
city: Macquarie University
country: Australia
facility: Research Site
city: St Leonards
country: Australia
facility: Research Site
city: Belo Horizonte
country: Brazil
facility: Research Site
city: Brasilia
country: Brazil
facility: Research Site
city: Cachoeiro De Itapemirim
country: Brazil
facility: Research Site
city: Criciuma
country: Brazil
facility: Research Site
city: Curitiba
country: Brazil
facility: Research Site
city: Florianopolis
country: Brazil
facility: Research Site
city: Fortaleza
country: Brazil
facility: Research Site
city: Natal
country: Brazil
facility: Research Site
city: Pelotas
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Rio de Janeiro
country: Brazil
facility: Research Site
city: Salvador
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: São Jose do Rio Preto
country: Brazil
facility: Research Site
city: Săo Paulo
country: Brazil
facility: Research Site
city: Vitoria
country: Brazil
facility: Research Site
city: Calgary
country: Canada
facility: Research Site
state: Alberta
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Providencia
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Temuco
country: Chile
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Harbin
country: China
facility: Research Site
city: Jinan
country: China
facility: Research Site
city: Nanjing
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
city: Brno
country: Czechia
facility: Research Site
city: Hradec Kralove
country: Czechia
facility: Research Site
city: Olomouc
country: Czechia
facility: Research Site
city: Praha 10
country: Czechia
facility: Research Site
city: Praha 5
country: Czechia
facility: Research Site
city: Praha 8
country: Czechia
facility: Research Site
city: Praha
country: Czechia
facility: Research Site
city: Bordeaux
country: France
facility: Research Site
city: Quimper
country: France
facility: Research Site
city: Toulouse Cedex 9
country: France
facility: Research Site
city: Villejuif
country: France
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Ulm
country: Germany
facility: Research Site
city: Hong Kong
country: Hong Kong
facility: Research Site
city: Shatin
country: Hong Kong
facility: Research Site
city: Bangalore
country: India
facility: Research Site
city: Belagavi
country: India
facility: Research Site
city: Jaipur
country: India
facility: Research Site
city: Mysore
country: India
facility: Research Site
city: Nashik
country: India
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Petah Tikva
country: Israel
facility: Research Site
city: Arezzo
country: Italy
facility: Research Site
city: Avellino
country: Italy
facility: Research Site
city: Bari
country: Italy
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Firenze
country: Italy
facility: Research Site
city: Meldola
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Padova
country: Italy
facility: Research Site
city: Reggio Emilia
country: Italy
facility: Research Site
city: Tricase
country: Italy
facility: Research Site
city: Verona
country: Italy
facility: Research Site
city: Daejeon
country: Korea, Republic of
facility: Research Site
city: Goyang-si
country: Korea, Republic of
facility: Research Site
city: Incheon
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Aguascalientes
country: Mexico
facility: Research Site
city: Monterrey
country: Mexico
facility: Research Site
city: Queretaro
country: Mexico
facility: Research Site
city: Toluca De Lerdo
country: Mexico
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Arnhem
country: Netherlands
facility: Research Site
city: Rotterdam
country: Netherlands
facility: Research Site
city: Gdansk
country: Poland
facility: Research Site
city: Gdynia
country: Poland
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Otwock
country: Poland
facility: Research Site
city: Poznan
country: Poland
facility: Research Site
city: Cluj Napoca
country: Romania
facility: Research Site
city: Cluj-Napoca
country: Romania
facility: Research Site
city: Craiova
country: Romania
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Cordoba
country: Spain
facility: Research Site
city: Coruña
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Majadahonda
country: Spain
facility: Research Site
city: Málaga
country: Spain
facility: Research Site
city: Pamplona
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Kaohsiung City
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Adana
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Edirne
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Karsiyaka
country: Turkey
facility: Research Site
city: Kazımkarabekir
country: Turkey
facility: Research Site
city: Dnipropetrovsk
country: Ukraine
facility: Research Site
city: Leicester
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Toni Choueiri
role: PRINCIPAL_INVESTIGATOR
References: