Papillary Renal Cell CarcinomaPhase 3SAMETANCT05043090
Savolitinib Plus Durvalumab Versus Sunitinib and Durvalumab Monotherapy in MET-Driven, Unresectable and Locally Advanced or Metastatic PRCC
A Phase 3 study testing savolitinib, durvalumab and sunitinib in people with Papillary Renal Cell Carcinoma, run by AstraZeneca at 139 sites in 25 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Papillary Renal Cell Carcinoma
- What is being tested?
- savolitinib, durvalumab and sunitinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 148 participants
- Where
- 139 sitesin 25 countries
- Study dates
- 28 Oct 2021to 1 Feb 2027
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
139 sites in 25 countries.
139 sites in 25 countries
Brazil18 sites
Research Site
Belo Horizonte, 30120-320
Research Site
Brasília, 70200-730
Research Site
Cachoeiro de Itapemirim, 29308-065
Research Site
Criciúma, 88811-508
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Curitiba, 81520-060
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Florianópolis, 88020-210
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Fortaleza, 60130-241
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Natal, 59075-740
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Pelotas, 96020-080
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Porto Alegre, 90020-090
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Porto Alegre, 90110-270
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Rio de Janeiro, 22250-905
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Salvador, 40050-410
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São Jose Do Rio Preto, 15090-000
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São Paulo, 01246-000
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São Paulo, 01327-001
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São Paulo, 05652-900
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Vitória, 29043-260
Spain13 sites
Research Site
A Coruña, 15006
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Barcelona, 08035
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Barcelona, 08036
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Barcelona, ?08041
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Córdoba, 14004
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Madrid, 28034
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Madrid, 28040
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Madrid, 28041
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Majadahonda, 28222
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Málaga, 29010
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Pamplona, 31008
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Seville, 41013
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Valencia, 46026
Italy12 sites
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Arezzo, 52100
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Avellino, 83100
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Bari, 70124
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Bologna, 40138
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Florence, 50134
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Meldola, 47014
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Milan, 20132
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Naples, 80131
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Padova, 35128
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Reggio Emilia, 42123
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Tricase, 73039
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Verona, 37134
China11 sites
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Beijing, 100039
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Changsha, 410011
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Changsha, 410013
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Chongqing, 400030
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Harbin, 150049
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Jinan, 250012
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Nanjing, 210029
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Shanghai, 200032
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Shenyang, 110042
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Tianjin, 300060
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Zhengzhou, 450008
Turkey (Türkiye)11 sites
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Adana, 01120
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Ankara, 06100
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Ankara, 06200
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Ankara, 06590
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Cordaleo, 35575
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Edirne, 22030
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Istanbul, 32098
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Istanbul, 34218
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Istanbul, 34722
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Izmir, 35040
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Kazımkarabekir, 01230
Argentina8 sites
Research Site
CABA, C1426ANZ
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Ciudad Autónoma Buenos Aires, 1125
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Ciudad de Buenos Aires, C1120AAT
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Ciudad de Buenos Aires, C1181ACH
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Córdoba, 5000
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La Plata, 1900
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Rosario, S2002KDS
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San Miguel de Tucumán, T4000IAK
Czechia7 sites
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Brno, 625 00
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Hradec Králové, 500 05
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Olomouc, 775 20
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Prague, 100 34
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Prague, 140 59
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Prague, 15000
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Prague, 180 81
South Korea7 sites
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Daejeon, 35015
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Goyang-si, 10408
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Incheon, 405-760
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Seoul, 03080
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Seoul, 03722
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Seoul, 05505
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Seoul, 06351
India5 sites
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Bangalore, 560027
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Belagavi, 590010
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Jaipur, 302002
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Mysore, 570001
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Nashik, 422004
Poland5 sites
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Gdansk, 80-952
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Gdynia, 81-519
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Krakow, 30-348
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Otwock, 05-400
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Poznan, 60-569
Chile4 sites
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Providencia, 7510032
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Santiago, 7500653
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Santiago, 8420383
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Temuco, 4810561
France4 sites
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Bordeaux, 33075
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Quimper, 29107
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Toulouse, 31059
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Villejuif, 94800
Germany4 sites
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Hamburg, 20246
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Hanover, 30625
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München, 81377
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Ulm, 89081
Mexico4 sites
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Aguascalientes, 20230
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Monterrey, 64460
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Querétaro, 76090
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Toluca, 50090
Australia3 sites
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Box Hill, 3128
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Macquarie University, 2109
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St Leonards, 2065
Canada3 sites
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Calgary, Alberta, T2N 4N2
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Montreal, Quebec, H3T 1E2
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Montreal, Quebec, H4A 3J1
Netherlands3 sites
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Amsterdam, 1105 AZ
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Arnhem, 6815 AD
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Rotterdam, 3045 PM
Romania3 sites
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Cluj-Napoca, 400015
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Cluj-Napoca, 400641
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Craiova, 200094
Taiwan3 sites
Research Site
Kaohsiung City, 83301
Research Site
Taichung, 40705
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Tainan, 704
United Kingdom3 sites
Research Site
Leicester, LE1 5WW
Research Site
London, EC1A 7BE
Research Site
London, SW3 6JJ
United States2 sites
Research Site
Boston, Massachusetts, 02215
Research Site
New York, New York, 10065
About this study
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)
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).
Read the 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.
- Conditions
- Papillary Renal Cell Carcinoma
- Being tested
- savolitinib, durvalumab, sunitinib
- Keywords
- Locally, Advanced, Metastatic, Carcinoma, Savolitinib, Sunitinib, Durvalumab, MET Driven, Papillary Renal Cell Carcinoma, Renal Cell
- Medical subject headings
- Carcinoma, Renal Cell, Neoplasm Metastasis, Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
savolitinibDrug
Also called AZD6094, HMPL-504, volitinib
Tablets : 3 × 200 mg tablets once daily
durvalumabDrug
Also called MEDI4736
Concentrate for solution for IV infusion : 1500 mg durvalumab every 4 weeks
sunitinibDrug
Also called Sutent, SU11248
Capsules : 2 x 25mg capsules once daily 4 weeks on, 2 weeks off
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | savolitinib 600mg plus durvalumab 1500mg Receives: Drug: savolitinib; Drug: durvalumab |
| Arm B | Active comparator | sunitinib 50mg Receives: Drug: sunitinib |
| Arm C | Experimental | durvalumab 1500mg Receives: Drug: durvalumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Approximately 28 months post first subject randomized
Secondary outcomes (13)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Approximately 28 months post first subject randomized
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2021
- Study start28 Oct 2021
- Primary completion31 Dec 2025
- Study completion1 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Papillary Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 148 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Toni Choueiri, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05043090
- Sponsor's protocol ID
- D5086C00001
- Other IDs
- 2022-503105-38-00, 2021-000336-55
- Acronym
- SAMETA
- Status last verified
- Oct 2026
- First submitted
- 11 Aug 2021
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
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.
PubMed 41861260