Savolitinib vs. Sunitinib in MET-driven PRCC.

A Phase III, Open Label, Randomised, Controlled, Multi-Centre Study To Assess the Efficacy and Safety of Savolitinib Versus Sunitinib in Patients With MET-Driven, Unresectable and Locally Advanced, Or Metastatic Papillary Renal Cell Carcinoma (PRCC)

This study is designed for patients diagnosed with MET-driven, unresectable and locally advanced or metastatic Papillary Renal Cell Carcinoma. The purpose of this study is to see if an investigational new anti-cancer medication, savolitinib, is effective in treating patients with MET-driven PRCC, how it compares with another medication frequently used to treat this disease called sunitinib, and what side effects it might cause.

Study Overview

• Status: Active, not recruiting
• Conditions: Kidney Neoplasms; Carcinoma, Renal Cell; Urologic Neoplasms; Neoplasms by Site; Kidney Diseases; Carcinoma; Enzyme Inhibitors; Protein Kinase Inhibitors
• Intervention / Treatment: Drug: Savolitinib; Drug: Sunitinib

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Barretos, Brazil, 14784-400
    • Research Site
  • Curitiba, Brazil, 81520-060
    • Research Site
  • Passo Fundo, Brazil, 99010-080
    • Research Site
  • Pelotas, Brazil, 096015-280
    • Research Site
  • Porto Alegre, Brazil, 90610-000
    • Research Site
  • Porto Alegre, Brazil, 91350-200
    • Research Site
  • Porto Alegre, Brazil, 90050-170
    • Research Site
  • Rio de Janeiro, Brazil, 22793-080
    • Research Site
  • Sao Paulo, Brazil, 01323-903
    • Research Site
  • São José do Rio Preto, Brazil, 15090-000
    • Research Site
  • São Paulo, Brazil, 01246-000
    • Research Site
• France
  • Bordeaux, France, 33000
    • Research Site
  • Vandoeuvre les Nancy, France, 54519
    • Research Site
  • Villejuif, France, 94805
    • Research Site
• Italy
  • Arezzo, Italy, 52100
    • Research Site
  • Meldola, Italy, 47014
    • Research Site
  • Milano, Italy, 20133
    • Research Site
  • Modena, Italy, 41100
    • Research Site
  • Orbassano, Italy, 10043
    • Research Site
  • Pavia, Italy, 27100
    • Research Site
  • Roma, Italy, 00152
    • Research Site
• Korea, Republic of
  • Daejeon, Korea, Republic of, 35015
    • Research Site
  • Goyang-si, Korea, Republic of, 10408
    • Research Site
  • Hwasun-gun, Korea, Republic of, 58128
    • Research Site
  • Incheon, Korea, Republic of, 21565
    • Research Site
  • Seoul, Korea, Republic of, 05505
    • Research Site
  • Seoul, Korea, Republic of, 03080
    • Research Site
  • Seoul, Korea, Republic of, 06273
    • Research Site
  • Seoul, Korea, Republic of, 6351
    • Research Site
  • Seoul, Korea, Republic of, 120-752
    • Research Site
• Russian Federation
  • Krasnoyarsk, Russian Federation, 660133
    • Research Site
  • Moscow, Russian Federation, 115478
    • Research Site
  • Moscow, Russian Federation, 115522
    • Research Site
  • Moscow, Russian Federation, 105077
    • Research Site
  • Moscow, Russian Federation, RU-121356
    • Research Site
  • Murmansk, Russian Federation, 183047
    • Research Site
  • Nizhnii Novgorod, Russian Federation, 603109
    • Research Site
  • Obninsk, Russian Federation, 249036
    • Research Site
  • Omsk, Russian Federation, 644013
    • Research Site
  • Saint Petersburg, Russian Federation, 195271
    • Research Site
  • Sankt-Peterburg, Russian Federation, 196603
    • Research Site
  • St. Petersburg, Russian Federation, 194017
    • Research Site
  • Volgograd, Russian Federation, 400138
    • Research Site
• Ukraine
  • Dnipro, Ukraine, 49102
    • Research Site
  • Dnipro, Ukraine, 49005
    • Research Site
  • Ivano-Frankivsk, Ukraine, 76018
    • Research Site
  • Kharkiv Region, Ukraine, 61070
    • Research Site
  • Kyiv, Ukraine, 03115
    • Research Site
  • Kyiv, Ukraine, 03022
    • Research Site
  • Odesa, Ukraine, 65055
    • Research Site
  • Sumy, Ukraine, 40022
    • Research Site
• United States
  • California
    • La Jolla, California, United States, 92093
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Research Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Research Site
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • Research Site
  • New York
    • New York, New York, United States, 10021
      • Research Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed PRCC, which is unresectable/locally advanced or metastatic with measurable disease as per RECIST 1.1. Patients with papillary urothelial carcinoma or renal pelvis cancer of the kidney are not considered PRCC and are not eligible.
2. Confirmation of MET-driven PRCC without co-occurring FH or VHL mutations from an FFPE tumour sample using the sponsor-designated central laboratory validated NGS assay
3. Patients who have received no prior systemic therapy as well as those who have received prior systemic therapy for PRCC in the advanced setting.* Patients can be treatment-naïve, or previously treated, but cannot have previously received sunitinib or a MET inhibitor. Patients who have received prior systemic therapy must have had disease progression in soft tissue disease or bone within 6 months of the last dose of the most recent systemic therapy
4. Adequate haematological, renal, cardiac and liver functions
5. Karnofsky performance status ≥ 80

Exclusion Criteria:

1. Most recent cytotoxic chemotherapy, immunotherapy, chemo-immunotherapy, or investigational agents <28 days from the date of randomisation. Most recent non cytotoxic targeted therapy <14 days from the date of randomisation.
2. Prior treatment with a MET inhibitor (e.g. foretinib, crizotinib, cabozantinib, onartuzumab or previous savolitinib) or sunitinb.
3. Treatment with strong inducers or inhibitors of CYP3A4 or strong inhibitors of CYP1A2, taken within 2 weeks or not possible to be stopped for at least 2 week before the date of randomisation. Herbal medications cannot be taken within 7 days of the date of randomisation (3 weeks for St John's wort).
4. Wide field radiotherapy administered ≤28 days or limited field radiation for palliation ≤7 days prior to the date of randomisation
5. Major surgical procedures ≤28 days of randomisation or minor surgical procedures ≤7 days. No waiting is required following port-a-cath placement.
6. Previously untreated brain metastases
7. Serious active infection or gastrointestinal disease
8. Presence of other active cancers, or history of treatment for invasive cancer within the last 5 years.
9. Mean resting QTcF >470 msec for women and >450 msec for men on the Part 2 screening triplicate ECGs or factors that may increase the risk of QTcF prolongation such as chronic hypokalaemia not correctable with supplements, congenital or familial long QT syndrome, or family history of unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval and cause Torsades de Pointes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Savolitinib; See: intervention description	Drug: Savolitinib; 600 mg (400 mg if <50 kg) by mouth (PO) with a meal once daily (QD), continuously; Other Names: AZD6094 (HMPL-504)/Volitinib
Active Comparator: Sunitinib; See: intervention description	Drug: Sunitinib; 50 mg by mouth (PO) once daily (QD), with or w/o food, 4 weeks on/2weeks off

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) by Blinded Independent Central Review (BICR)	Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Progressive Disease (PD): >= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of NTLs or a new lesion. PFS is the time from date of randomisation until the date of PD (defined by Recist 1.1 and confirmed by BICR) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression.	RECIST tumour assessments every 6 weeks from randomisation until disease progression as defined by Recist 1.1 and confirmed by BICR.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Time between the date of randomisation and the date of death due to any cause.	RECIST tumour assessments every 6 weeks from randomisation until disease progression as defined by Recist 1.1 and confirmed by BICR.
Objective Response Rate (ORR) by BICR	Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. ORR is the percentage of patients with at least 1 visit response of CR or PR prior to progression or any further therapy.	RECIST tumour assessments every 6 weeks from randomisation until disease progression as defined by Recist 1.1 and confirmed by BICR.
Duration of Response (DoR) by BICR	Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. DoR is the time from the date of first documented response until the date of documented progression or death in the absence of disease progression.	RECIST tumour assessments every 6 weeks from randomisation until disease progression as defined by Recist 1.1 and confirmed by BICR.
Disease Control Rate (DCR) at 6 Months by BICR	Disease control rate at 6 months is defined as the percentage of patients who have a best objective response of Complete Response or Partial Response in that period or who have demonstrated Stable Disease for a minimum interval of 23 weeks.	RECIST tumour assessments every 6 weeks from randomisation until disease progression as defined by Recist 1.1 and confirmed by BICR.
Disease Control Rate (DCR) at 12 Months by BICR	Disease control rate at 12 months is defined as the percentage of patients who have a best objective response of complete responses or partial responses in that period or who have demonstrated stable disease for a minimum interval of 47 weeks.	RECIST tumour assessments every 6 weeks from randomisation until disease progression as defined by Recist 1.1 and confirmed by BICR.

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Hutchinson MediPharma (HMP)
• Investigators: Principal Investigator: Toni K Choueiri, MD, Dana-Farber Cancer Institute

Publications and helpful links

General Publications

• Maia MC, Salgia M, Pal SK. Harnessing cell-free DNA: plasma circulating tumour DNA for liquid biopsy in genitourinary cancers. Nat Rev Urol. 2020 May;17(5):271-291. doi: 10.1038/s41585-020-0297-9. Epub 2020 Mar 17.
• Choueiri TK, Heng DYC, Lee JL, Cancel M, Verheijen RB, Mellemgaard A, Ottesen LH, Frigault MM, L'Hernault A, Szijgyarto Z, Signoretti S, Albiges L. Efficacy of Savolitinib vs Sunitinib in Patients With MET-Driven Papillary Renal Cell Carcinoma: The SAVOIR Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Aug 1;6(8):1247-1255. doi: 10.1001/jamaoncol.2020.2218. Erratum In: JAMA Oncol. 2020 Sep 1;6(9):1473.

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2017
• Primary Completion (Actual): August 18, 2019
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: February 9, 2017
• First Submitted That Met QC Criteria: March 21, 2017
• First Posted (Actual): March 27, 2017

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Savolitinib; AZD6094; Papillary Renal Cell Cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Urogenital Neoplasms; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Neoplasms; Kidney Neoplasms; Carcinoma, Renal Cell; Kidney Diseases; Carcinoma; Urologic Neoplasms; Neoplasms by Site; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sunitinib
• Other Study ID Numbers: D5082C00003; 2016-004108-73 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No