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

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)

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.

Study Overview

• Status: Completed
• Conditions: GIST
• Intervention / Treatment: Drug: avapritinib; Drug: regorafenib

• Study Type: Interventional
• Enrollment (Actual): 476
• Phase: Phase 3

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia
    • Flinders Medical Center
  • Clayton, Australia
    • Monash Health
  • Garran, Australia
    • The Canberra Hospital
• Austria
  • Wien, Austria
    • AKH, Klinik f. Innere Med. I, Onkologie
• Belgium
  • Brussels, Belgium
    • Institut Jules Bordet
  • Leuven, Belgium
    • Leuven Cancer Institute
• Canada
  • Montréal, Canada
    • Jewish General Hospital
  • Alberta
    • Edmonton, Alberta, Canada
      • Cross Cancer Institute
  • Ontario
    • Toronto, Ontario, Canada, M5G 1L7
      • University Health Network
• China
  • Beijing, China
    • Chinese PLA General Hospital
  • Beijing, China
    • Beijing Cancer hospital
  • Chengdu, China
    • West China Hospital Sichuan University
  • Chongqing, China
    • The First Affiliated Hospital of Chongqing Medical University
  • Fuzhou, China
    • Fujian Medical University Union Hospital
  • Guangzhou, China
    • The First Affiliated Hospital of Sun Yat-sen University
  • Guangzhou, China
    • The Sixth Affiliated Hospital of Sun Yat-sen University
  • Hangzhou, China
    • The First Affiliated Hospital, Zhejiang University
  • Harbin, China
    • Harbin Medical University Cancer Hospital
  • Nanchang, China
    • The First Affiliated Hospital of Nanchang Medical University
  • Nanning, China
    • Guangxi Medical University Affiliated Tumor Hospital & Oncology Medical College
  • Qingdao, China
    • The Affiliated Hospital of Qingdao University
  • Shanghai, China
    • Fudan University Shanghai Cancer Center
  • Shanghai, China
    • Fudan University Zhongshan Hospital
  • Shanghai, China
    • Shanghai Jiaotong University School of Medicine, Renji Hospital
  • Shenyang, China
    • Liaoning cancer Hospital & Institute
  • Tianjin, China
    • Tianjin Cancer Hospital
  • Wuhan, China
    • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
  • Ürümqi, China
    • Affiliated Cancer Hospital of Xinjiang Medical University
• Czechia
  • Olomouc, Czechia
    • Onkologická klinika Fakultní nemocnice Olomouc
  • Praha, Czechia
    • Fackultni Nemocnice v Motole
• France
  • Bordeaux, France
    • Institut Bergonie
  • Lille, France
    • Centre Oscar Lambret
  • Lyon, France, 69008
    • UNICANCER - Lyon, Centre Léon-Bérard
  • Marseille, France
    • Institute Paoli Calmettes
  • Marseille, France
    • La Timone University hospital
  • Paris, France
    • Institut Curie
  • Saint-Herblain, France
    • Centre René Gauducheau
  • Villejuif, France
    • Gustave Roussy Cancer Campus
• Germany
  • Bad Saarow, Germany
    • Helios Klinikum Bad Saarow
  • Berlin, Germany
    • Helios Klinikum Berlin-Buch
  • Dresden, Germany
    • Medizinische Fakultät Carl Gustav Carus
  • Essen, Germany
    • Universitaetsklindum Essen
  • Frankfurt, Germany
    • Universitätsklinikum Frankfurt
  • Lubeck, Germany
    • Studienzentrale GbR Lübecker Onkologische Schwerpunktpraxis Dres. med. Uthgenannt
  • Mannheim, Germany
    • Rupercht-Karls-Universitaet Heidelberg
• Hungary
  • Budapest, Hungary
    • Fovarosi Onkormanyzat Szent Laszlo Korhaz
  • Budapest, Hungary
    • Magyar Honvedseg Egeszsegugyi Kozpont Onkologiai Osztaly
  • Debrecen, Hungary
    • Medical Oncology University Debrecen
  • Pécs, Hungary
    • University of Pecs
• Italy
  • Bologna, Italy
    • Azienda Ospedaliero Universitaria Sant'Orsola Malpighi
  • Candiolo, Italy
    • Candiolo Cancer Institute - FPO, IRCCS
  • Firenze, Italy
    • AOUC Azienda Ospedaliero - Universitaria Careggi
  • Milano, Italy
    • Istituto Europeo di Oncologia
  • Milano, Italy
    • Fondazione IRCCS Istituto Nazionale dei Tumori Milano
  • Palermo, Italy
    • Universita degli Studi di Palermo - Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
  • Roma, Italy
    • Campus Bio-Medico - Oncology Medica
• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • Severance Hospital
  • Gyeong Gi-do
    • Suwon-si, Gyeong Gi-do, Korea, Republic of
      • Ajou University Hospital
• Netherlands
  • Amsterdam, Netherlands
    • Nederlands Kanker Instituut - Antoni van Leeuwenhoek Ziekenhuis
  • Nijmegen, Netherlands
    • Radboud University Medical Center
  • Rotterdam, Netherlands
    • Erasmus Medical Center
• Poland
  • Kraków, Poland
    • Sanodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwesytecki w Krakowie, Oddzial Kliniczny Onkologii
  • Olsztyn, Poland
    • Samodzielny Publiczny Zaklad Opieki Zdrowotnej MSWiA z W-MCO
  • Warszawa, Poland
    • Maria Skodowska Curie Memorial Cancer Centre and Institute of Oncology
  • Wrocław, Poland
    • Dolnoslaskie Centrum Onkologii we Wrocawiu
• Singapore
  • Singapore, Singapore
    • National Cancer Centre Singapore
• Spain
  • Barcelona, Spain
    • Hospital De La Santa Creu I Sant Pau
  • Barcelona, Spain
    • Vall d'Hebron
  • Barcelona, Spain
    • Institut Català d'Oncologia - Hospital Duran i Reynals
  • Madrid, Spain
    • Hospital La Paz
  • Madrid, Spain
    • Hospital Universitario Puerta de Hierro
  • Madrid, Spain
    • Hospital Universitario Gregorio Maranon
  • Sevilla, Spain
    • Hospital Virgen Del Rocio
  • Valencia, Spain
    • Fundacion Instituto Valenciano de Oncologia, Servicio de Oncologia
  • Zaragoza, Spain
    • Hospital Universitario Miguel Servet
• Sweden
  • Lund, Sweden
    • Skånes University Hospital
• United Kingdom
  • Glasgow, United Kingdom
    • Beatson West of Scotland Cancer Centre
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden Hospital
  • London, United Kingdom
    • Guy's Hospital
  • Manchester, United Kingdom
    • The Christie NHS Foundation Trust
  • Sheffield, United Kingdom
    • Sheffield Teaching Hospitals NHS Foundation Trust
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Cancer Center
  • California
    • Santa Monica, California, United States, 90404
      • UCLA Hematology/Oncology - Santa Monica
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
    • Boulder, Colorado, United States, 80303
      • Rocky Mountain Cancer Centers
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital Center - Oncology and Hematology
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Cancer Center
    • Miami, Florida, United States, 33146
      • University of Miami
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30341
      • Northside Hospital
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medical Center
    • Chicago, Illinois, United States, 60611
      • Northwestern Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
  • Missouri
    • Saint Louis, Missouri, United States, 63130
      • Washington University in Saint Louis
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU - Knight Cancer Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology
  • Texas
    • Dallas, Texas, United States, 75246
      • USO - Texas Oncology
    • Denton, Texas, United States, 76210
      • Texas Oncology - Denton South
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson
    • Waco, Texas, United States, 76712
      • Texas Oncology - Waco
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
    • Spokane, Washington, United States, 99216
      • Summit Cancer Centers
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin - Froedtert Hospital

Participation Criteria

Eligibility Criteria

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

Description

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.

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: avapritinib; 300 mg PO QD	Drug: avapritinib; Avapritinib tablets for oral administration. Avapritinib will be dosed at 300 mg once daily, continuously.; Other Names: 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 Names: Stivarga

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	24 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) Determined by Central Radiology Assessment Per mRECIST, Version 1.1	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	24 Months
Overall Survival (OS) in Patients With Advanced GIST Treated With Avapritinib Compared to Patients Treated With Regorafenib	To evaluate overall survival (OS) in patients with advanced GIST treated with avapritinib compared to patients treated with regorafenib	24 Months
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	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.	Difference between baseline and week 12 of treatment

Collaborators and Investigators

• Sponsor: Blueprint Medicines Corporation

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2018
• Primary Completion (Actual): March 9, 2020
• Study Completion (Actual): September 15, 2021

Study Registration Dates

• First Submitted: March 7, 2018
• First Submitted That Met QC Criteria: March 13, 2018
• First Posted (Actual): March 14, 2018

Study Record Updates

• Last Update Posted (Actual): October 6, 2022
• Last Update Submitted That Met QC Criteria: September 9, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: gastrointestinal stromal tumor; PDGFRA; Avapritinib; BLU-285; BLU 285; BLUE-285; BLUE 285; 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; cancer gist; gist cancer; Other Relapsed or Refractory Solid Tumors
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors
• Other Study ID Numbers: BLU-285-1303

Drug and device information, study documents

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