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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

22 Oct 2021 → ongoing

Decision date (initial)

2024-06-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca, Sweden

External identifiers

EU CT number

2022-503105-38-00

EudraCT number

2021-000336-55

ClinicalTrials.gov

NCT05043090

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacogenomic, Pharmacogenetic, Efficacy, Safety, Therapy

To demonstrate the effectiveness of savolitinib plus durvalumab relative to sunitinib by assessment of progression-free survival (PFS) in participants with MET-driven, unresectable and locally advanced or metastatic PRCC.

Secondary objectives 1

1. a. To demonstrate the effectiveness of savolitinib plus durvalumab relative to sunitinib in participants with MET-driven, unresectable and locally advanced or metastatic PRCC by the assessment of: - overall survival (OS) - objective response rate (ORR) - duration of response (DoR) - disease control rate (DCR) at 24 and 48 weeks - time from randomisation to second progression or death (PFS2) b. To demonstrate the effectiveness of savolitinib plus durvalumab relative to durvalumab monotherapy in participants with MET-driven, unresectable and locally advanced or metastatic PRCC by assessment of: - ORR - DoR - PFS c. To assess patient-reported symptoms, functioning, and HRQoL in participants with MET-driven, unresectable and locally advanced or metastatic PRCC treated with savolitinib plus durvalumab relative to sunitinib d. To evaluate the PK of savolitinib and durvalumab in participants with MET-driven, unresectable and locally advanced or metastatic PRCC.

Conditions and MedDRA coding

MET-driven, unresectable and locally advanced or metastatic Papillary Renal Cell Carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Histologically confirmed unresectable and locally advanced or metastatic PRCC
2. PRCC must be centrally confirmed as MET-driven using a sponsor designated central laboratory validated NGS assay
3. No prior systemic anti-cancer treatment in the metastatic setting; no prior exposure to MET inhibitors, Durvalumab or Sunitinib in any setting
4. Karnofsky Score ≥70
5. At least one lesion, not previously irradiated, that can be accurately measured at baseline
6. Adequate organ and bone marrow function
7. Life expectancy minimum of 12 weeks
8. Adequate coagulation parameters
9. Mandatory provision of an FFPE tumour sample to assess the MET driven PRCC

Exclusion criteria 6

1. 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
2. Spinal cord compression or brain metastases, unless asymptomatic and stable on treatment for at least 14 days prior to study intervention
3. 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
4. Active infection including HIV, TB, HBV and HCV
5. Active or prior documented autoimmune or inflammatory disorders
6. Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS is defined as time from randomisation until disease progression per RECIST 1.1 as assessed by blinded independent central review (BICR), or death due to any cause.

Secondary endpoints 9

1. a. and b. : 1. OS is defined as time from randomisation until the date of death due to any cause.
2. a. and b. : 2. ORR is defined as the proportion of participants who have a complete response (CR) or partial response (PR) as determined by BICR per RECIST 1.1.
3. a. and b. : 3. DoR will be 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.
4. a. and b. : 4. DCR at 24 or 48 weeks is 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.
5. a. and b. : 5. PFS2 will be defined as time from randomisation to the earliest of the progression event (following the initial progression), subsequent to the first subsequent therapy or death.
6. a. and b. : 6. PFS is defined as time from randomisation until disease progression per RECIST 1.1 as assessed by blinded independent central review (BICR), or death due to any cause.
7. c. Time to deterioration and change from baseline in symptoms, functioning, and HRQoL
8. d. The measures of interest are as follows: 1. participants randomised to savolitinib plus durvalumab: plasma concentration of savolitinib and its metabolites pre-dose (Ctrough) andpost-dose (C1h and C3h), serum concentration of durvalumab pre-dose (Ctrough) and at the end of infusion (Cmax)
9. d.: 2. participants randomised to durvalumab monotherapy: serum concentration of durvalumab pre-dose (Ctrough) and at the end of infusion (Cmax)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 4

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

Ines Lenic

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca, Information Center

Third parties 12

Locations

8 EU/EEA countries · 49 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 111 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications