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

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)

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 Overview

• Status: Active, not recruiting
• Conditions: Papillary Renal Cell Carcinoma
• Intervention / Treatment: Drug: savolitinib; Drug: durvalumab; Drug: sunitinib

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objective radiological PD per RECIST 1.1 is assessed by the investigator, unacceptable toxicity occurs, consent is withdrawn or another discontinuation criterion is met.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

• Study Type: Interventional
• Enrollment (Actual): 148
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • CABA, Argentina, C1426ANZ
    • Research Site
  • Ciudad Autónoma Buenos Aires, Argentina, 1125
    • Research Site
  • Ciudad de Buenos Aires, Argentina, C1181ACH
    • Research Site
  • Ciudad de Buenos Aires, Argentina, C1120AAT
    • Research Site
  • La Plata, Argentina, 1900
    • Research Site
  • Rosario, Argentina, S2002KDS
    • Research Site
  • San Miguel de Tucumán, Argentina, T4000IAK
    • Research Site
• Australia
  • Box Hill, Australia, 3128
    • Research Site
  • Macquarie University, Australia, 2109
    • Research Site
• Brazil
  • Belo Horizonte, Brazil, 30120-320
    • Research Site
  • Brasília, Brazil, 70200-730
    • Research Site
  • Cachoeiro de Itapemirim, Brazil, 29308-065
    • Research Site
  • Criciúma, Brazil, 88811-508
    • Research Site
  • Curitiba, Brazil, 81520-060
    • Research Site
  • Florianópolis, Brazil, 88020-210
    • Research Site
  • Fortaleza, Brazil, 60130-241
    • Research Site
  • Natal, Brazil, 59075-740
    • Research Site
  • Pelotas, Brazil, 96020-080
    • Research Site
  • Porto Alegre, Brazil, 90020-090
    • Research Site
  • Porto Alegre, Brazil, 90110-270
    • Research Site
  • Rio de Janeiro, Brazil, 22250-905
    • Research Site
  • Salvador, Brazil, 40050-410
    • Research Site
  • São Jose Do Rio Preto, Brazil, 15090-000
    • Research Site
  • São Paulo, Brazil, 01246-000
    • Research Site
  • São Paulo, Brazil, 05652-900
    • Research Site
  • São Paulo, Brazil, 01327-001
    • Research Site
  • Vitória, Brazil, 29043-260
    • Research Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Research Site
    • Montreal, Quebec, Canada, H3T 1E2
      • Research Site
• Chile
  • Providencia, Chile, 7510032
    • Research Site
  • Santiago, Chile, 8420383
    • Research Site
  • Santiago, Chile, 7500653
    • Research Site
  • Temuco, Chile, 4810561
    • Research Site
• China
  • Beijing, China, 100039
    • Research Site
  • Changsha, China, 410013
    • Research Site
  • Changsha, China, 410011
    • Research Site
  • Chongqing, China, 400030
    • Research Site
  • Harbin, China, 150049
    • Research Site
  • Jinan, China, 250012
    • Research Site
  • Nanjing, China, 210029
    • Research Site
  • Shanghai, China, 200032
    • Research Site
  • Shenyang, China, 110042
    • Research Site
  • Tianjin, China, 300060
    • Research Site
  • Zhengzhou, China, 450008
    • Research Site
• Czechia
  • Brno, Czechia, 625 00
    • Research Site
  • Hradec Králové, Czechia, 500 05
    • Research Site
  • Olomouc, Czechia, 775 20
    • Research Site
  • Prague, Czechia, 15000
    • Research Site
  • Prague, Czechia, 100 34
    • Research Site
  • Prague, Czechia, 140 59
    • Research Site
  • Prague, Czechia, 180 81
    • Research Site
• France
  • Bordeaux, France, 33075
    • Research Site
  • Quimper, France, 29107
    • Research Site
  • Toulouse, France, 31059
    • Research Site
  • Villejuif, France, 94800
    • Research Site
• Germany
  • Hamburg, Germany, 20246
    • Research Site
  • Hanover, Germany, 30625
    • Research Site
  • München, Germany, 81377
    • Research Site
  • Ulm, Germany, 89081
    • Research Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Research Site
  • Shatin, Hong Kong, 00000
    • Research Site
• India
  • Bangalore, India, 560027
    • Research Site
  • Belagavi, India, 590010
    • Research Site
  • Jaipur, India, 302002
    • Research Site
  • Mysore, India, 570001
    • Research Site
  • Nashik, India, 422004
    • Research Site
• Israel
  • Haifa, Israel, 91096
    • Research Site
  • Petah Tikva, Israel, 49100
    • Research Site
• Italy
  • Arezzo, Italy, 52100
    • Research Site
  • Avellino, Italy, 83100
    • Research Site
  • Bari, Italy, 70124
    • Research Site
  • Bologna, Italy, 40138
    • Research Site
  • Florence, Italy, 50134
    • Research Site
  • Meldola, Italy, 47014
    • Research Site
  • Milan, Italy, 20132
    • Research Site
  • Naples, Italy, 80131
    • Research Site
  • Padova, Italy, 35128
    • Research Site
  • Reggio Emilia, Italy, 42123
    • Research Site
  • Tricase, Italy, 73039
    • Research Site
  • Verona, Italy, 37134
    • Research Site
• Mexico
  • Aguascalientes, Mexico, 20230
    • Research Site
  • Monterrey, Mexico, 64460
    • Research Site
  • Querétaro, Mexico, 76090
    • Research Site
  • Toluca, Mexico, 50090
    • Research Site
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Research Site
  • Arnhem, Netherlands, 6815 AD
    • Research Site
  • Rotterdam, Netherlands, 3045 PM
    • Research Site
• Poland
  • Gdansk, Poland, 80-952
    • Research Site
  • Gdynia, Poland, 81-519
    • Research Site
  • Krakow, Poland, 30-348
    • Research Site
  • Otwock, Poland, 05-400
    • Research Site
  • Poznan, Poland, 60-569
    • Research Site
• Romania
  • Cluj-Napoca, Romania, 400015
    • Research Site
  • Cluj-Napoca, Romania, 400641
    • Research Site
  • Craiova, Romania, 200094
    • Research Site
• Singapore
  • Singapore, Singapore, 169610
    • Research Site
• South Korea
  • Daejeon, South Korea, 35015
    • Research Site
  • Goyang-si, South Korea, 10408
    • Research Site
  • Incheon, South Korea, 405-760
    • Research Site
  • Seoul, South Korea, 03080
    • Research Site
  • Seoul, South Korea, 03722
    • Research Site
  • Seoul, South Korea, 05505
    • Research Site
  • Seoul, South Korea, 06351
    • Research Site
• Spain
  • A Coruña, Spain, 15006
    • Research Site
  • Barcelona, Spain, 08035
    • Research Site
  • Barcelona, Spain, 08036
    • Research Site
  • Barcelona, Spain, ?08041
    • Research Site
  • Córdoba, Spain, 14004
    • Research Site
  • Madrid, Spain, 28034
    • Research Site
  • Madrid, Spain, 28041
    • Research Site
  • Madrid, Spain, 28040
    • Research Site
  • Majadahonda, Spain, 28222
    • Research Site
  • Málaga, Spain, 29010
    • Research Site
  • Pamplona, Spain, 31008
    • Research Site
  • Seville, Spain, 41013
    • Research Site
  • Valencia, Spain, 46026
    • Research Site
• Taiwan
  • Kaohsiung City, Taiwan, 83301
    • Research Site
  • Taichung, Taiwan, 40705
    • Research Site
  • Tainan, Taiwan, 704
    • Research Site
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01120
    • Research Site
  • Ankara, Turkey (Türkiye), 06100
    • Research Site
  • Ankara, Turkey (Türkiye), 06590
    • Research Site
  • Ankara, Turkey (Türkiye), 06200
    • Research Site
  • Cordaleo, Turkey (Türkiye), 35575
    • Research Site
  • Edirne, Turkey (Türkiye), 22030
    • Research Site
  • Istanbul, Turkey (Türkiye), 34722
    • Research Site
  • Istanbul, Turkey (Türkiye), 32098
    • Research Site
  • Istanbul, Turkey (Türkiye), 34218
    • Research Site
  • Izmir, Turkey (Türkiye), 35040
    • Research Site
  • Kazımkarabekir, Turkey (Türkiye), 01230
    • Research Site
• Ukraine
  • Dnipropetrovsk, Ukraine, 49005
    • Research Site
• United Kingdom
  • Leicester, United Kingdom, LE1 5WW
    • Research Site
  • London, United Kingdom, EC1A 7BE
    • Research Site
  • London, United Kingdom, SW3 6JJ
    • Research Site
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Research Site
  • New York
    • New York, New York, United States, 10065
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; savolitinib 600mg plus durvalumab 1500mg	Drug: savolitinib; Tablets : 3 × 200 mg tablets once daily; Other Names: AZD6094, HMPL-504, volitinib; Drug: durvalumab; Concentrate for solution for IV infusion : 1500 mg durvalumab every 4 weeks; Other Names: MEDI4736
Active Comparator: Arm B; sunitinib 50mg	Drug: sunitinib; Capsules : 2 x 25mg capsules once daily 4 weeks on, 2 weeks off; Other Names: Sutent, SU11248
Experimental: Arm C; durvalumab 1500mg	Drug: durvalumab; Concentrate for solution for IV infusion : 1500 mg durvalumab every 4 weeks; Other Names: MEDI4736

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	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 Measures

Outcome Measure	Measure Description	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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Toni Choueiri, Dana-Farber Cancer Institute

Publications and helpful links

General Publications

• Jackson-Spence F, Larkin J, Patel P, Valderrama BP, Rodriguez-Vida A, Glen H, Thistlethwaite FC, Ralph C, Srinivasan G, Mendez-Vidal MJ, Childress M, Li W, Boyle P, Gasco A, Markovets A, Hartmaier R, Ackerman C, Szabados BE, Priyadarshini G, Jamal F, Powles T, Suarez C. CALYPSO: Final Results of Savolitinib and Durvalumab Combination in Metastatic Papillary Renal Cancer. J Clin Oncol. 2026 Apr 20;44(12):1076-1082. doi: 10.1200/JCO-25-01840. Epub 2026 Mar 20.

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2021
• Primary Completion (Actual): December 31, 2025
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: August 11, 2021
• First Submitted That Met QC Criteria: September 9, 2021
• First Posted (Actual): September 13, 2021

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Carcinoma; Locally; Advanced; Metastatic; Savolitinib; Durvalumab; Sunitinib; Renal Cell; MET Driven; Papillary Renal Cell Carcinoma
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Neoplastic Processes; Urologic Neoplasms; Kidney Neoplasms; Pathological Conditions, Signs and Symptoms; Carcinoma; Neoplasm Metastasis; Carcinoma, Renal Cell; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Indoles; Pyrroles; Sunitinib; durvalumab; 1-(1-(imidazo(1,2-a)pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-(1,2,3)triazolo(4,5-b)pyrazine
• Other Study ID Numbers: D5086C00001; 2021-000336-55 (EudraCT Number); 2022-503105-38-00 (Registry Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD 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.

• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No