Savolitinib Plus Durvalumab Versus Sunitinib and Durvalumab Monotherapy in MET-Driven, Unresectable and Locally Advanced or Metastatic PRCC
- Conditions
- Papillary Renal Cell Carcinoma
- Interventions
- Registration Number
- NCT05043090
- Lead Sponsor
- AstraZeneca
- 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objective radiological PD per RECIST 1.1 is assessed by the investigator, unacceptable toxicity occurs, consent is withdrawn or another discontinuation criterion is met.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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 148
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A savolitinib savolitinib 600mg plus durvalumab 1500mg Arm A durvalumab savolitinib 600mg plus durvalumab 1500mg Arm B sunitinib sunitinib 50mg Arm C durvalumab durvalumab 1500mg
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) /savolitinib plus durvalumab relative to sunitinib Approximately 28 months post first subject randomized 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.
- Secondary Outcome Measures
Name Time Method Evaluation of the PK of savolitinib pre-dose Approximately 28 months post first subject randomized 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.
Evaluation of the PK of savolitinib post-dose Approximately 28 months post first subject randomized Plasma concentration of savolitinib and its metabolites post-dose (C1h and C3h) in participants randomised to savolitinib plus durvalumab.
Progression-Free Survival (PFS) /savolitinib plus durvalumab relative to durvalumab monotherapy Approximately 28 months post first subject randomized 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.Evaluation of the PK of durvalumab pre-dose Approximately 28 months post first subject randomized 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.
Evaluation of the PK of durvalumab / Cmax (maximum plasma concentration) Approximately 28 months post first subject randomized Serum concentration of durvalumab at the end of infusion (Cmax) in participants randomised to savolitinib plus durvalumab or durvalumab monotherapy.
Overall Survival (OS) /savolitinib plus durvalumab relative to sunitinib Approximately 28 months and approximately 42 months post first subject randomized 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.
Objective Response Rate (ORR) / savolitinib plus durvalumab relative to sunitinib Approximately 28 months post first subject randomized Defined as the proportion of participants who have a Complete Response (CR) or Partial Response (PR) as determined by BICR per RECIST 1.1.
Disease Control Rate (DCR) at 24 and 48 weeks /savolitinib plus durvalumab relative to sunitinib Approximately 28 months post first subject randomized 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.
Duration of Response (DoR) / savolitinib plus durvalumab relative to sunitinib Approximately 28 months post first subject randomized 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.
Time from randomisation to second progression or death (PFS2) /savolitinib plus durvalumab relative to sunitinib Approximately 28 months and 42 months post first subject randomized Defined as time from randomisation to the earliest of the progression event (following the initial progression), subsequent to the first subsequent therapy or death.
Assessment of patient-reported symptoms, functioning, and HRQoL /savolitinib plus durvalumab relative to sunitinib Approximately 28 months post first subject randomized Time to deterioration and change from baseline in symptoms, functioning, and HRQoL as measured by FKSI-19.
Objective Response Rate (ORR) / savolitinib plus durvalumab relative to durvalumab monotherapy Approximately 28 months post first subject randomized Defined as the proportion of participants who have a Complete Response (CR) or Partial Response (PR) as determined by BICR per RECIST 1.1
Duration of Response (DoR) / savolitinib plus durvalumab relative to durvalumab monotherapy Approximately 28 months post first subject randomized 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.
Trial Locations
- Locations (1)
Research Site
🇬🇧London, United Kingdom