(VOYAGER) Study of Avapritinib vs Regorafenib in Patients With Locally Advanced Unresectable or Metastatic GIST

• ClinicalTrials.gov Identifier: NCT03465722
• Recruitment Status: Completed
• First Posted: March 14, 2018
• Results First Posted: May 14, 2021
• Last Update Posted: October 6, 2022
• Sponsor: Blueprint Medicines Corporation
• Information provided by (Responsible Party): Blueprint Medicines Corporation

Study Description

Brief Summary:

This is an open-label, randomized, Phase 3 study in patients with locally advanced unresectable or metastatic GIST (advanced GIST) of avapritinib (also known as BLU-285) versus regorafenib in patients previously treated with imatinib and 1 or 2 other TKIs.

Condition or disease	Intervention/treatment	Phase
GIST	Drug: avapritinib; Drug: regorafenib	Phase 3

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Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 476 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An International, Multicenter, Open-label, Randomized, Phase 3 Study of BLU-285 vs Regorafenib in Patients With Locally Advanced Unresectable or Metastatic Gastrointestinal Stromal Tumor (GIST)
• Actual Study Start Date: March 26, 2018
• Actual Primary Completion Date: March 9, 2020
• Actual Study Completion Date: September 15, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: avapritinib; 300 mg PO QD	Drug: avapritinib; Avapritinib tablets for oral administration. Avapritinib will be dosed at 300 mg once daily, continuously.; Other Name: BLU-285
Active Comparator: regorafenib; 160 mg PO QD	Drug: regorafenib; Regorafenib tablets for oral administration. Regorafenib will be dosed at 160 mg once daily for 3 weeks out of every 4 weeks (ie. 3 weeks on/1 week off).; Other Name: Stivarga

Outcome Measures

Primary Outcome Measures :

1. Efficacy of Avapritinib Based on Progression-free Survival (PFS) Determined by Central Radiological Assessment Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST), Version 1.1 [ Time Frame: 24 Months ]
   To demonstrate the efficacy of avapritinib based on progression-free survival (PFS) determined by central radiological assessment per modified Response Evaluation Criteria in Solid Tumors (mRECIST), version 1.1 in patients with advanced GIST following 2 or 3 regimens of prior treatment with a tyrosine kinase inhibitor (TKI), including imatinib, compared to patients treated with regorafenib. A progressively growing tumor must meet the following criteria: a) the target lesions must be greater or equal to 2cm in size and be a new GIST active lesion or b) the target lesions must be expanding on at least 2 sequential imaging studies.

Secondary Outcome Measures :

1. Objective Response Rate (ORR) Determined by Central Radiology Assessment Per mRECIST, Version 1.1 [ Time Frame: 24 Months ]
   To evaluate objective response rate (ORR) determined by central radiology assessment per mRECIST, version 1.1 in patients with advanced GIST treated with avapritinib compared to patients treated with regorafenib. A complete response (CR) per modified Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) is defined as complete disappearance of all target lesions. A partial response (PR) is defined as at least 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters. Overall Response (OR) = CR + PR
2. Overall Survival (OS) in Patients With Advanced GIST Treated With Avapritinib Compared to Patients Treated With Regorafenib [ Time Frame: 24 Months ]
   To evaluate overall survival (OS) in patients with advanced GIST treated with avapritinib compared to patients treated with regorafenib
3. European Organisation for Research and Treatment of Cancer Quality of Life (EORTC-QLQ-30). Change in Individual Scores in Patients With Advanced GIST Treated With Avapritinib Compared to Patients Treated With Regorafenib [ Time Frame: Difference between baseline and week 12 of treatment ]
   The Global Health Status Score is derived from question 29 and 30 on the EORTC-QLQ-C30 tool. The change in score was assessed between baseline and week 12 in patients treated with advanced GIST treated with avapritinib compared to patients treated with regorafenib. The Global Health Status Score score range is 0 to 100 with a higher score indicating better global health status. A positive change indicates improvement in global health status.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Patients who are ≥ 18 years of age.
2. Patients who have histologically confirmed metastatic or unresectable GIST.
3. Patients who received imatinib and 1 or 2 other TKIs as prior treatment regimens. Patients who experienced intolerance to prior therapies must have objective disease progression prior to enrollment onto BLU-285-1303 study.
4. Patients who have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1.

Exclusion Criteria:

1. Patients who have received prior treatment with avapritinib or regorafenib.
2. Patients who have previously received more than 3 different TKI treatment regimens.
3. Patients who are known to be both V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) and platelet-derived growth factor receptor alpha (PDGRFα) wild type.
4. Patients who received any systemic anticancer therapy within 1 week before the first dose of study drug.
5. Patients who have clinically significant cardiovascular disease
6. Patients have experienced arterial thrombotic or embolic events within 6 months before the first dose of study drug, or venous thrombotic events within 14 days of the first dose of study drug
7. Patients who have experienced any hemorrhage or bleeding event NCI CTCAE version 5.0 Grade 3 or higher within 4 weeks before the first dose of study drug
8. Patients who have a known risk of intracranial bleeding, or a history of intracranial bleeding within 1 year prior to the first dose of study drug
9. Patients who have a symptomatic non-healing wound, ulcer, gastrointestinal perforation, or bone fracture.
10. Patients who have poor organ function as defined by laboratory parameters specified in the protocol.
11. Patients who have received neutrophil growth factor support within 14 days of first dose of study drug.
12. Patients who require therapy with a concomitant medication that is a strong inhibitor or strong inducer of CYP3A4.
13. Patients who have had a major surgical procedure within 14 days of the first dose of study drug. Patient has significant traumatic injury within 28 days before the first dose of study drug.
14. Patients who have a history of another primary malignancy that has been diagnosed or required therapy within 3 years before first dose of study drug.
15. Patients who have a history of a seizure disorder requiring anti-seizure medication.
16. Patients who have metastases to the brain.
17. Patients who have a QT interval corrected using Fridericia's formula (QTcF) of > 450 msec.
18. Women who are unwilling, if not postmenopausal or surgically sterile, to abstain from sexual intercourse or employ highly effective contraception from the time of the first dose of study drug and for at least 60 days after the last dose of study drug. Men who are unwilling, if not surgically sterile, to abstain from sexual intercourse or employ highly effective contraception from the time of the first dose of study drug and for at least 90 days after the last dose of study drug.
19. Women who are pregnant.
20. Women who are breastfeeding.
21. Patients who have prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality as determined by the investigator.

Contacts and Locations

Locations

United States, Arizona

Mayo Clinic Cancer Center

Phoenix, Arizona, United States, 85054

United States, California

UCLA Hematology/Oncology - Santa Monica

Santa Monica, California, United States, 90404

United States, Colorado

University of Colorado Hospital

Aurora, Colorado, United States, 80045

Rocky Mountain Cancer Centers

Boulder, Colorado, United States, 80303

United States, District of Columbia

Washington Hospital Center - Oncology and Hematology

Washington, District of Columbia, United States, 20010

United States, Florida

Mayo Clinic Cancer Center

Jacksonville, Florida, United States, 32224

University of Miami

Miami, Florida, United States, 33146

Moffitt Cancer Center

Tampa, Florida, United States, 33612

United States, Georgia

Northside Hospital

Atlanta, Georgia, United States, 30341

United States, Illinois

Northwestern Medicine

Chicago, Illinois, United States, 60611

The University of Chicago Medical Center

Chicago, Illinois, United States, 60637

United States, Massachusetts

Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, Michigan

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States, 48109

United States, Minnesota

Mayo Clinic Cancer Center

Rochester, Minnesota, United States, 55905

United States, Missouri

Washington University in Saint Louis

Saint Louis, Missouri, United States, 63130

United States, New York

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27710

United States, Ohio

Ohio State University

Columbus, Ohio, United States, 43210

United States, Oregon

OHSU - Knight Cancer Institute

Portland, Oregon, United States, 97239

United States, Pennsylvania

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States, 19111

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States, 15232

United States, Tennessee

Tennessee Oncology

Nashville, Tennessee, United States, 37203

United States, Texas

USO - Texas Oncology

Dallas, Texas, United States, 75246

Texas Oncology - Denton South

Denton, Texas, United States, 76210

University of Texas MD Anderson

Houston, Texas, United States, 77030

Texas Oncology - Waco

Waco, Texas, United States, 76712

United States, Utah

Huntsman Cancer Institute

Salt Lake City, Utah, United States, 84112

United States, Washington

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States, 98109

Summit Cancer Centers

Spokane, Washington, United States, 99216

United States, Wisconsin

Medical College of Wisconsin - Froedtert Hospital

Milwaukee, Wisconsin, United States, 53226

Australia

Flinders Medical Center

Adelaide, Australia

Monash Health

Clayton, Australia

The Canberra Hospital

Garran, Australia

Austria

AKH, Klinik f. Innere Med. I, Onkologie

Wien, Austria

Belgium

Institut Jules Bordet

Brussels, Belgium

Leuven Cancer Institute

Leuven, Belgium

Canada, Alberta

Cross Cancer Institute

Edmonton, Alberta, Canada

Canada, Ontario

University Health Network

Toronto, Ontario, Canada, M5G 1L7

Canada

Jewish General Hospital

Montréal, Canada

China

Beijing Cancer Hospital

Beijing, China

Chinese PLA General Hospital

Beijing, China

West China Hospital Sichuan University

Chengdu, China

The First Affiliated Hospital of Chongqing Medical University

Chongqing, China

Fujian Medical University Union Hospital

Fuzhou, China

The First Affiliated Hospital of Sun Yat-sen University

Guangzhou, China

The Sixth Affiliated Hospital of Sun Yat-Sen University

Guangzhou, China

The First Affiliated Hospital, Zhejiang University

Hangzhou, China

Harbin Medical University Cancer Hospital

Harbin, China

The First Affiliated Hospital of Nanchang Medical University

Nanchang, China

Guangxi Medical University Affiliated Tumor Hospital & Oncology Medical College

Nanning, China

The Affiliated Hospital of Qingdao University

Qingdao, China

Fudan University Shanghai Cancer Center

Shanghai, China

Fudan University Zhongshan Hospital

Shanghai, China

Shanghai Jiaotong University School of Medicine, Renji Hospital

Shanghai, China

Liaoning Cancer Hospital & Institute

Shenyang, China

Tianjin Cancer Hospital

Tianjin, China

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, China

Affiliated Cancer Hospital of Xinjiang Medical University

Ürümqi, China

Czechia

Onkologická klinika Fakultní nemocnice Olomouc

Olomouc, Czechia

Fackultni Nemocnice v Motole

Praha, Czechia

France

Institut Bergonié

Bordeaux, France

Centre Oscar Lambret

Lille, France

UNICANCER - Lyon, Centre Léon-Bérard

Lyon, France, 69008

Institute Paoli Calmettes

Marseille, France

La Timone University Hospital

Marseille, France

Institut Curie

Paris, France

Centre Rene Gauducheau

Saint-Herblain, France

Gustave Roussy Cancer Campus

Villejuif, France

Germany

HELIOS Klinikum Bad Saarow

Bad Saarow, Germany

HELIOS Klinikum Berlin-Buch

Berlin, Germany

Medizinische Fakultät Carl Gustav Carus

Dresden, Germany

Universitaetsklindum Essen

Essen, Germany

Universitätsklinikum Frankfurt

Frankfurt, Germany

Studienzentrale GbR Lübecker Onkologische Schwerpunktpraxis Dres. med. Uthgenannt

Lubeck, Germany

Rupercht-Karls-Universitaet Heidelberg

Mannheim, Germany

Hungary

Fovarosi Onkormanyzat Szent Laszlo Korhaz

Budapest, Hungary

Magyar Honvédség Egészségügyi Központ Onkológiai Osztály

Budapest, Hungary

Medical Oncology University Debrecen

Debrecen, Hungary

University of Pécs

Pécs, Hungary

Italy

Azienda Ospedaliero Universitaria Sant'Orsola Malpighi

Bologna, Italy

Candiolo Cancer Institute - FPO, IRCCS

Candiolo, Italy

AOUC Azienda Ospedaliero - Universitaria Careggi

Firenze, Italy

Fondazione IRCCS Istituto Nazionale dei Tumori Milano

Milano, Italy

Istituto Europeo di Oncologia

Milano, Italy

Universita degli Studi di Palermo - Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

Palermo, Italy

Campus Bio-Medico - Oncology Medica

Roma, Italy

Korea, Republic of

Ajou University Hospital

Suwon-si, Gyeong Gi-do, Korea, Republic of

Asan Medical Center

Seoul, Korea, Republic of

Samsung Medical Center

Seoul, Korea, Republic of

Seoul National University Hospital

Seoul, Korea, Republic of

Severance Hospital

Seoul, Korea, Republic of

Netherlands

Nederlands Kanker Instituut - Antoni Van Leeuwenhoek Ziekenhuis

Amsterdam, Netherlands

Radboud University Medical Center

Nijmegen, Netherlands

Erasmus Medical Center

Rotterdam, Netherlands

Poland

Sanodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwesytecki w Krakowie, Oddzial Kliniczny Onkologii

Kraków, Poland

Samodzielny Publiczny Zaklad Opieki Zdrowotnej MSWiA z W-MCO

Olsztyn, Poland

Maria Skodowska Curie Memorial Cancer Centre and Institute of Oncology

Warszawa, Poland

Dolnoslaskie Centrum Onkologii we Wrocawiu

Wrocław, Poland

Singapore

National Cancer Centre Singapore

Singapore, Singapore

Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Institut Català d'Oncologia - Hospital Duran i Reynals

Barcelona, Spain

Vall d'Hebron

Barcelona, Spain

Hospital La Paz

Madrid, Spain

Hospital Universitario Gregorio Marañón

Madrid, Spain

Hospital Universitario Puerta de Hierro

Madrid, Spain

Hospital Virgen del Rocio

Sevilla, Spain

Fundacion Instituto Valenciano de Oncologia, Servicio de Oncologia

Valencia, Spain

Hospital Universitario Miguel Servet

Zaragoza, Spain

Sweden

Skanes University Hospital

Lund, Sweden

United Kingdom

Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom

The Royal Marsden Hospital

London, United Kingdom, SW3 6JJ

Guy's Hospital

London, United Kingdom

The Christie NHS Foundation Trust

Manchester, United Kingdom

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, United Kingdom

Sponsors and Collaborators

Blueprint Medicines Corporation

  Study Documents (Full-Text)

Documents provided by Blueprint Medicines Corporation:

Study Protocol  [PDF] June 20, 2019

Statistical Analysis Plan  [PDF] February 1, 2020

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kang YK, George S, Jones RL, Rutkowski P, Shen L, Mir O, Patel S, Zhou Y, von Mehren M, Hohenberger P, Villalobos V, Brahmi M, Tap WD, Trent J, Pantaleo MA, Schoffski P, He K, Hew P, Newberry K, Roche M, Heinrich MC, Bauer S. Avapritinib Versus Regorafenib in Locally Advanced Unresectable or Metastatic GI Stromal Tumor: A Randomized, Open-Label Phase III Study. J Clin Oncol. 2021 Oct 1;39(28):3128-3139. doi: 10.1200/JCO.21.00217. Epub 2021 Aug 3.

Gebreyohannes YK, Wozniak A, Zhai ME, Wellens J, Cornillie J, Vanleeuw U, Evans E, Gardino AK, Lengauer C, Debiec-Rychter M, Sciot R, Schoffski P. Robust Activity of Avapritinib, Potent and Highly Selective Inhibitor of Mutated KIT, in Patient-derived Xenograft Models of Gastrointestinal Stromal Tumors. Clin Cancer Res. 2019 Jan 15;25(2):609-618. doi: 10.1158/1078-0432.CCR-18-1858. Epub 2018 Oct 1.

• Responsible Party: Blueprint Medicines Corporation
• ClinicalTrials.gov Identifier: NCT03465722
• Other Study ID Numbers: BLU-285-1303
• First Posted: March 14, 2018
• Results First Posted: May 14, 2021
• Last Update Posted: October 6, 2022
• Last Verified: September 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Blueprint Medicines Corporation:

Other Relapsed or Refractory Solid Tumors; cancer gist; gastrointestinal stromal tumor; gist cancer; BLU-285; BLU 285; BLUE-285; BLUE 285; Avapritinib; GIST imatinib relapse; GIST gleevec relapse; GIST KIT; GIST relapse; GIST refractory; GIST imatinib intolerance; GIST TKI treatment; GIST tyrosine kinase inhibitor treatment; GIST TKI; GIST tyrosine kinase inhibitor; Advanced GIST; GIST mutations; GIST treatments; Blueprint GIST; Relapsed GIST clinical trial; Refractory GIST clinical trial; KIT-mutant GIST; PDGFRA

Additional relevant MeSH terms:

Gastrointestinal Stromal Tumors; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases