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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT05043090




Registration number
NCT05043090
Ethics application status
Date submitted
11/08/2021
Date registered
13/09/2021
Date last updated
13/09/2021

Titles & IDs
Public title
Savolitinib Plus Durvalumab Versus Sunitinib and Durvalumab Monotherapy in MET-Driven, Unresectable and Locally Advanced or Metastatic PRCC
Scientific 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)
Secondary ID [1] 0 0
2021-000336-55
Secondary ID [2] 0 0
D5086C00001
Universal Trial Number (UTN)
Trial acronym
SAMETA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Papillary Renal Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - savolitinib
Treatment: Drugs - durvalumab
Treatment: Drugs - sunitinib

Experimental: Arm A - savolitinib 600mg plus durvalumab 1500mg

Active Comparator: Arm B - sunitinib 50mg

Experimental: Arm C - durvalumab 1500mg


Treatment: Drugs: savolitinib
Tablets : 3 × 200 mg tablets once daily

Treatment: Drugs: durvalumab
Concentrate for solution for IV infusion : 1500 mg durvalumab every 4 weeks

Treatment: Drugs: sunitinib
Capsules : 2 x 25mg capsules once daily 4 weeks on, 2 weeks off

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Approximately 28 months post first subject randomized
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Approximately 28 months and approximately 42 months post first subject randomized
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Approximately 28 months post first subject randomized
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Approximately 28 months post first subject randomized
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Approximately 28 months post first subject randomized
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
Approximately 28 months and 42 months post first subject randomized
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
Approximately 28 months post first subject randomized
Secondary outcome [7] 0 0
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
Timepoint [7] 0 0
Approximately 28 months post first subject randomized
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
Approximately 28 months post first subject randomized
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
Approximately 28 months post first subject randomized
Secondary outcome [10] 0 0
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.
Timepoint [10] 0 0
Approximately 28 months post first subject randomized
Secondary outcome [11] 0 0
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.
Timepoint [11] 0 0
Approximately 28 months post first subject randomized
Secondary outcome [12] 0 0
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.
Timepoint [12] 0 0
Approximately 28 months post first subject randomized
Secondary outcome [13] 0 0
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.
Timepoint [13] 0 0
Approximately 28 months post first subject randomized

Eligibility
Key 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
Minimum age
18 Years
Maximum age
130 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- History of serious liver disease, with or without, normal LFTs, such as cirrhosis or
Wilson's disease

- 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Westmead
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
San Miguel de Tucuman
Country [2] 0 0
Brazil
State/province [2] 0 0
Porto Alegre
Country [3] 0 0
Czechia
State/province [3] 0 0
Brno
Country [4] 0 0
Czechia
State/province [4] 0 0
Hradec Kralove
Country [5] 0 0
Czechia
State/province [5] 0 0
Olomouc
Country [6] 0 0
Czechia
State/province [6] 0 0
Praha 10
Country [7] 0 0
Czechia
State/province [7] 0 0
Praha 5
Country [8] 0 0
Czechia
State/province [8] 0 0
Praha 8
Country [9] 0 0
Czechia
State/province [9] 0 0
Praha
Country [10] 0 0
France
State/province [10] 0 0
Nice
Country [11] 0 0
France
State/province [11] 0 0
Villejuif
Country [12] 0 0
Italy
State/province [12] 0 0
Firenze
Country [13] 0 0
Korea, Republic of
State/province [13] 0 0
Seoul
Country [14] 0 0
Mexico
State/province [14] 0 0
Aguascalientes
Country [15] 0 0
Mexico
State/province [15] 0 0
Monterrey
Country [16] 0 0
Mexico
State/province [16] 0 0
México
Country [17] 0 0
Mexico
State/province [17] 0 0
Queretaro
Country [18] 0 0
Poland
State/province [18] 0 0
Gdansk
Country [19] 0 0
Poland
State/province [19] 0 0
Gdynia
Country [20] 0 0
Poland
State/province [20] 0 0
Otwock
Country [21] 0 0
Spain
State/province [21] 0 0
Barcelona
Country [22] 0 0
Taiwan
State/province [22] 0 0
Tainan
Country [23] 0 0
Turkey
State/province [23] 0 0
Ankara
Country [24] 0 0
United Kingdom
State/province [24] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
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)
Trial website
https://clinicaltrials.gov/show/NCT05043090
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Toni Choueiri
Address 0 0
Dana-Farber Cancer Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
AstraZeneca Clinical Study Information Center
Address 0 0
Country 0 0
Phone 0 0
1-877-240-9479
Fax 0 0
Email 0 0
information.center@astrazeneca.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT05043090