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

Titre officiel

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)

Sommaire:

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)

Description de l'essai

Primary Outcome:

• Progression-Free Survival (PFS) /savolitinib plus durvalumab relative to sunitinib

• Overall Survival (OS) /savolitinib plus durvalumab relative to sunitinib
• Objective Response Rate (ORR) / savolitinib plus durvalumab relative to sunitinib
• Duration of Response (DoR) / savolitinib plus durvalumab relative to sunitinib
• Disease Control Rate (DCR) at 24 and 48 weeks /savolitinib plus durvalumab relative to sunitinib
• Time from randomisation to second progression or death (PFS2) /savolitinib plus durvalumab relative to sunitinib
• Assessment of patient-reported symptoms, functioning, and HRQoL /savolitinib plus durvalumab relative to sunitinib
• Objective Response Rate (ORR) / savolitinib plus durvalumab relative to durvalumab monotherapy
• Duration of Response (DoR) / savolitinib plus durvalumab relative to durvalumab monotherapy
• Progression-Free Survival (PFS) /savolitinib plus durvalumab relative to durvalumab monotherapy
• Evaluation of the PK of savolitinib pre-dose
• Evaluation of the PK of savolitinib post-dose
• Evaluation of the PK of durvalumab pre-dose
• Evaluation of the PK of durvalumab / Cmax (maximum plasma concentration)

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.

Voir cet essai sur ClinicalTrials.gov