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

Ведущий спонсор: AstraZeneca

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)

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objective radiological PD per RECIST 1.1 is assessed by the investigator, unacceptable toxicity occurs, consent is withdrawn or another discontinuation criterion is met.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

• Papillary Renal Cell Carcinoma

Тип вмешательства: Drug

Название вмешательства: savolitinib

Описание: Tablets : 3 × 200 mg tablets once daily

Этикетка Arm Group: Arm A

Другое имя: AZD6094, HMPL-504, volitinib

Тип вмешательства: Drug

Название вмешательства: durvalumab

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

Другое имя: MEDI4736

Тип вмешательства: Drug

Название вмешательства: sunitinib

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

Этикетка Arm Group: Arm B

Другое имя: Sutent, SU11248

Критерии:

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

Пол:

All

Минимальный возраст:

18 Years

Максимальный возраст:

130 Years

Здоровые волонтеры:

No

Фамилия: AstraZeneca Clinical Study Information Center

Телефон: 1-877-240-9479

Argentina

Australia

Brazil

Canada

Chile

Czechia

France

Germany

Hong Kong

India

Israel

Italy

Korea, Republic of

Mexico

Netherlands

Poland

Romania

Russian Federation

Singapore

Spain

Taiwan

Turkey

Ukraine

United Kingdom

United States

2022-01-01

Тип: Sponsor

• Locally
• Advanced
• Metastatic
• Carcinoma
• Savolitinib
• Sunitinib
• Durvalumab
• MET Driven
• Papillary Renal Cell Carcinoma
• Renal Cell

• Carcinoma
• Carcinoma, Renal Cell

Метка: Arm A

Тип: Experimental

Описание: savolitinib 600mg plus durvalumab 1500mg

Метка: Arm B

Тип: Active Comparator

Описание: sunitinib 50mg

Метка: Arm C

Тип: Experimental

Описание: durvalumab 1500mg

Распределение: Randomized

Модель вмешательства: Parallel Assignment

Первичное назначение: Treatment

Маскировка: None (Open Label)