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Savolitinib Plus Durvalumab Versus Sunitinib and Durvalumab Monotherapy in MET-Driven, Unresectable and Locally Advanced or Metastatic PRCC (SAMETA)

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ClinicalTrials.gov Identifier: NCT05043090
Recruitment Status : Recruiting
First Posted : September 13, 2021
Last Update Posted : November 29, 2021
Sponsor:
Information provided by (Responsible Party):
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)

Condition or disease Intervention/treatment Phase
Papillary Renal Cell Carcinoma Drug: savolitinib Drug: durvalumab Drug: sunitinib Phase 3

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objective radiological PD per RECIST 1.1 is assessed by the investigator, unacceptable toxicity occurs, consent is withdrawn or another discontinuation criterion is met.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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : October 28, 2021
Estimated Primary Completion Date : March 28, 2024
Estimated Study Completion Date : June 9, 2025


Arm Intervention/treatment
Experimental: Arm A
savolitinib 600mg plus durvalumab 1500mg
Drug: savolitinib
Tablets : 3 × 200 mg tablets once daily
Other Name: AZD6094, HMPL-504, volitinib

Drug: durvalumab
Concentrate for solution for IV infusion : 1500 mg durvalumab every 4 weeks
Other Name: MEDI4736

Active Comparator: Arm B
sunitinib 50mg
Drug: sunitinib
Capsules : 2 x 25mg capsules once daily 4 weeks on, 2 weeks off
Other Name: Sutent, SU11248

Experimental: Arm C
durvalumab 1500mg
Drug: durvalumab
Concentrate for solution for IV infusion : 1500 mg durvalumab every 4 weeks
Other Name: MEDI4736




Primary Outcome Measures :
  1. Progression-Free Survival (PFS) /savolitinib plus durvalumab relative to sunitinib [ Time Frame: 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 :
  1. Overall Survival (OS) /savolitinib plus durvalumab relative to sunitinib [ Time Frame: 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.

  2. Objective Response Rate (ORR) / savolitinib plus durvalumab relative to sunitinib [ Time Frame: 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.

  3. Duration of Response (DoR) / savolitinib plus durvalumab relative to sunitinib [ Time Frame: 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.

  4. Disease Control Rate (DCR) at 24 and 48 weeks /savolitinib plus durvalumab relative to sunitinib [ Time Frame: 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.

  5. Time from randomisation to second progression or death (PFS2) /savolitinib plus durvalumab relative to sunitinib [ Time Frame: 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.

  6. Assessment of patient-reported symptoms, functioning, and HRQoL /savolitinib plus durvalumab relative to sunitinib [ Time Frame: Approximately 28 months post first subject randomized ]
    Time to deterioration and change from baseline in symptoms, functioning, and HRQoL as measured by FKSI-19.

  7. Objective Response Rate (ORR) / savolitinib plus durvalumab relative to durvalumab monotherapy [ Time Frame: 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

  8. Duration of Response (DoR) / savolitinib plus durvalumab relative to durvalumab monotherapy [ Time Frame: 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.

  9. Progression-Free Survival (PFS) /savolitinib plus durvalumab relative to durvalumab monotherapy [ Time Frame: 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.


  10. Evaluation of the PK of savolitinib pre-dose [ Time Frame: 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.

  11. Evaluation of the PK of savolitinib post-dose [ Time Frame: 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.

  12. Evaluation of the PK of durvalumab pre-dose [ Time Frame: 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.

  13. Evaluation of the PK of durvalumab / Cmax (maximum plasma concentration) [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05043090


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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Sponsors and Collaborators
AstraZeneca
Investigators
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Principal Investigator: Toni Choueiri Dana-Farber Cancer Institute
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT05043090    
Other Study ID Numbers: D5086C00001
2021-000336-55 ( EudraCT Number )
First Posted: September 13, 2021    Key Record Dates
Last Update Posted: November 29, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Locally
Advanced
Metastatic
Carcinoma
Savolitinib
Sunitinib
Durvalumab
MET Driven
Papillary Renal Cell Carcinoma
Renal Cell
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Durvalumab
Sunitinib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action