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

NCT ID: NCT05043090

Last Updated: 2025-05-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

148 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-10-28

Study Completion Date

2025-10-30

Brief Summary

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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

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objective radiological PD per RECIST 1.1 is assessed by the investigator, unacceptable toxicity occurs, consent is withdrawn or another discontinuation criterion is met.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

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Papillary Renal Cell Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A

savolitinib 600mg plus durvalumab 1500mg

Group Type EXPERIMENTAL

savolitinib

Intervention Type DRUG

Tablets : 3 × 200 mg tablets once daily

durvalumab

Intervention Type DRUG

Concentrate for solution for IV infusion : 1500 mg durvalumab every 4 weeks

Arm B

sunitinib 50mg

Group Type ACTIVE_COMPARATOR

sunitinib

Intervention Type DRUG

Capsules : 2 x 25mg capsules once daily 4 weeks on, 2 weeks off

Arm C

durvalumab 1500mg

Group Type EXPERIMENTAL

durvalumab

Intervention Type DRUG

Concentrate for solution for IV infusion : 1500 mg durvalumab every 4 weeks

Interventions

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savolitinib

Tablets : 3 × 200 mg tablets once daily

Intervention Type DRUG

durvalumab

Concentrate for solution for IV infusion : 1500 mg durvalumab every 4 weeks

Intervention Type DRUG

sunitinib

Capsules : 2 x 25mg capsules once daily 4 weeks on, 2 weeks off

Intervention Type DRUG

Other Intervention Names

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AZD6094, HMPL-504, volitinib MEDI4736 Sutent, SU11248

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

130 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Toni Choueiri

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

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Research Site

Boston, Massachusetts, United States

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New York, New York, United States

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Buenos Aires, , Argentina

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CABA, , Argentina

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Ciudad Autonoma Buenos Aires, , Argentina

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Ciudad Autónoma Buenos Aires, , Argentina

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Córdoba, , Argentina

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La Plata, , Argentina

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Rosario, , Argentina

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San Miguel de Tucumán, , Argentina

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Box Hill, , Australia

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Macquarie University, , Australia

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St Leonards, , Australia

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Belo Horizonte, , Brazil

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Brasília, , Brazil

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Cachoeiro de Itapemirim, , Brazil

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Criciúma, , Brazil

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Curitiba, , Brazil

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Florianópolis, , Brazil

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Fortaleza, , Brazil

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Natal, , Brazil

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Pelotas, , Brazil

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Porto Alegre, , Brazil

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Porto Alegre, , Brazil

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Rio de Janeiro, , Brazil

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Salvador, , Brazil

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São Jose Do Rio Preto, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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Săo Paulo, , Brazil

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Vitória, , Brazil

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Calgary, Alberta, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Providencia, , Chile

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Santiago, , Chile

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Santiago, , Chile

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Temuco, , Chile

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Beijing, , China

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Changsha, , China

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Changsha, , China

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Chongqing, , China

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Harbin, , China

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Jinan, , China

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Nanjing, , China

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Shanghai, , China

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Shenyang, , China

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Tianjin, , China

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Zhengzhou, , China

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Brno, , Czechia

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Hradec Králové, , Czechia

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Olomouc, , Czechia

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Prague, , Czechia

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Prague, , Czechia

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Prague, , Czechia

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Prague, , Czechia

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Bordeaux, , France

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Quimper, , France

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Toulouse, , France

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Villejuif, , France

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Hamburg, , Germany

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Hanover, , Germany

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München, , Germany

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Ulm, , Germany

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Hong Kong, , Hong Kong

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Shatin, , Hong Kong

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Bangalore, , India

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Belagavi, , India

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Jaipur, , India

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Mysore, , India

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Nashik, , India

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Haifa, , Israel

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Petah Tikva, , Israel

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Arezzo, , Italy

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Avellino, , Italy

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Bari, , Italy

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Bologna, , Italy

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Florence, , Italy

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Meldola, , Italy

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Milan, , Italy

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Napoli, , Italy

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Padua, , Italy

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Reggio Emilia, , Italy

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Tricase, , Italy

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Verona, , Italy

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Aguascalientes, , Mexico

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Monterrey, , Mexico

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Querétaro, , Mexico

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Toluca, , Mexico

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Amsterdam, , Netherlands

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Arnhem, , Netherlands

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Rotterdam, , Netherlands

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Gdansk, , Poland

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Gdynia, , Poland

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Krakow, , Poland

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Otwock, , Poland

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Poznan, , Poland

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Cluj-Napoca, , Romania

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Cluj-Napoca, , Romania

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Craiova, , Romania

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Singapore, , Singapore

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Daejeon, , South Korea

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Goyang-si, , South Korea

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Incheon, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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A Coruña, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Córdoba, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Majadahonda, , Spain

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Málaga, , Spain

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Pamplona, , Spain

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Seville, , Spain

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Valencia, , Spain

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Kaohsiung City, , Taiwan

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Taichung, , Taiwan

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Tainan City, , Taiwan

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Adana, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Edirne, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Karşıyaka, , Turkey (Türkiye)

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Kazımkarabekir, , Turkey (Türkiye)

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Dnipropetrovsk, , Ukraine

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Leicester, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Countries

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United States Argentina Australia Brazil Canada Chile China Czechia France Germany Hong Kong India Israel Italy Mexico Netherlands Poland Romania Singapore South Korea Spain Taiwan Turkey (Türkiye) Ukraine United Kingdom

Other Identifiers

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2022-503105-38-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

2021-000336-55

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D5086C00001

Identifier Type: -

Identifier Source: org_study_id

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