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Savolitinib Plus Durvalumab Versus Sunitinib and Durvalumab Monotherapy in MET-Driven, Unresectable and Locally Advanced or Metastatic PRCC
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).
Study details:
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objective radiological PD per RECIST 1. 1 is assessed by the investigator, unacceptable toxicity occurs, consent is withdrawn or another discontinuation criterion is met.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
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 18 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2021-10-28
Primary completion: 2025-06-30
Study completion finish: 2026-06-12
Study type
TREATMENT
Phase
PHASE3
Trial ID
NCT05043090
Intervention or treatment
DRUG: savolitinib
DRUG: durvalumab
DRUG: sunitinib
Conditions
- • Papillary Renal Cell Carcinoma
Find a site
Closest Location:
Research Site
Research sites nearby
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Research Site
Macquarie University, Not Specified, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Arm A
| DRUG: savolitinib
|
ACTIVE_COMPARATOR: Arm B
| DRUG: sunitinib
|
EXPERIMENTAL: Arm C
| DRUG: durvalumab
|
What is the study measuring?
Primary outcome
| Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
|---|---|---|
| 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 outcome
| Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
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