MET-driven, unresectable and locally advanced or metastatic Papillary Renal Cell Carcinoma MedDRA version: 24.1 Level: PT Classification code 10085663 Term: Clear cell papillary renal cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion 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 with no co-occurring FH mutation • 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 minimum of 12weeks • Adequate coagulation parameters • Mandatory provision of an FFPE tumour sample to assess the MET-driven PRCC without co-occurring FH mutation Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 120 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 80
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the effectiveness of savolitinib plus durvalumab relative to sunitinib by assessment of progression-free survival (PFS) in participants with MET-driven, unresectable and locally advanced or metastatic PRCC.;Secondary Objective: a. To demonstrate the effectiveness of savolitinib plus durvalumab relative to sunitinib in participants with MET-driven, unresectable and locally advanced or metastatic PRCC by the assessment of : - overall survival (OS) - objective response rate (ORR) - duration of response (DoR) - disease control rate (DCR) at 24 and 48 weeks - time from randomisation to second progression or death (PFS2) b. To demonstrate the effectiveness of savolitinib plus durvalumab relative to durvalumab monotherapy in participants with MET-driven, unresectable and locally advanced or metastatic PRCC by assessment of : - ORR - DoR - PFS c. To assess patient-reported symptoms, functioning, and HRQoL in participants with MET-driven, unresectable and locally advanced or metastatic PRCC treated with savolitinib plus durvalumab relative to sunitinib d. To evaluate the PK of savolitinib and durvalumab in participants with MET-driven, unresectable and locally advanced or metastatic PRCC.;Primary end point(s): PFS is defined as time from randomisation until disease progression per RECIST 1.1 as assessed by blinded independent central review (BICR), or death due to any cause. ;Timepoint(s) of evaluation of this end point: PFS is defined as time from date or randomized until date of objective disease progression or death. Tumor scan performed at baseline then every 6 weeks for the first 54 weeks then every 12 weeks. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): a. and b. : - OS is defined as time from randomisation until the date of death due to any cause. - ORR is defined as the proportion of participants who have a complete response (CR) or partial response (PR) as determined by BICR per RECIST 1.1. - DoR will be 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. - DCR at 24 or 48 weeks is 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. - PFS2 will be defined as time from randomisation to the earliest of the progression event (following the initial progression), subsequent to the first subsequent therapy or death. - PFS is defined as time from randomisation until disease progression per RECIST 1.1 as assessed by blinded independent central review (BICR), or death due to any cause. c. Time to deterioration and change from baseline in symptoms, functioning, and HRQoL as measured by FKSI-19. d. The measures of interest are as follows: - participants randomised to savolitinib plus durvalumab : plasma concentration of savolitinib and its metabolites pre-dose (Ctrough) and post-dose (C1h and C3h), serum concentration of durvalumab pre-dose (Ctrough) and at the end of infusion (Cmax) - participants randomised to durvalumab monotherapy : serum concentration of durvalumab pre-dose (Ctrough) and at the end of infusion (Cmax);Timepoint(s) of evaluation of this end point: a. and b. : - OS: date of death - ORR: first objective response (complete or partial) - DoR: first documented response until date of documented progression or death - DCR : 24 or 48 weeks after randomization - PFS2: the earliest of progression event subsequent to first subsequent therapy or death - PFS: disease progression or death These are planned to be analyzed at approximately 28 mon | — |
Countries
Argentina, Australia, Brazil, Canada, Chile, China, Czechia, Czech Republic, France, Germany, Hong Kong, India, Israel, Italy, Korea, Republic of, Mexico, Netherlands, Poland, Romania, Russian Federation, Singapore, Spain, Taiwan, Türkiye, Ukraine, United Kingdom, United States
Contacts
Public ContactInformation Center
AstraZeneca
Outcome results
None listed