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

NCT03465722 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: BLU-285-1303
• Study Type: interventional
• Target: 476
• Locations: 17 countries
• Sites: 111

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.

Conditions

GIST

Keywords

Other Relapsed or Refractory Solid Tumors; 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; cancer gist; gastrointestinal stromal tumor; gist cancer; PDGFRA

Outcome Measures

Primary Outcomes (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

  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 Outcomes (3)

• Objective Response Rate (ORR) Determined by Central Radiology Assessment Per mRECIST, Version 1.1

  24 Months

• 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

  Difference between baseline and week 12 of treatment

Study Arms (2)

avapritinib

EXPERIMENTAL

300 mg PO QD

Drug: avapritinib

regorafenib

ACTIVE COMPARATOR

160 mg PO QD

Drug: regorafenib

Interventions

avapritinib DRUG

Avapritinib tablets for oral administration. Avapritinib will be dosed at 300 mg once daily, continuously.

Also known as: BLU-285

avapritinib

regorafenib DRUG

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).

Also known as: Stivarga

regorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who are ≥ 18 years of age.
• Patients who have histologically confirmed metastatic or unresectable GIST.
• 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.
• Patients who have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1.

You may not qualify if:

• Patients who have received prior treatment with avapritinib or regorafenib.
• Patients who have previously received more than 3 different TKI treatment regimens.
• 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.
• Patients who received any systemic anticancer therapy within 1 week before the first dose of study drug.
• Patients who have clinically significant cardiovascular disease
• 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
• 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
• 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
• Patients who have a symptomatic non-healing wound, ulcer, gastrointestinal perforation, or bone fracture.
• Patients who have poor organ function as defined by laboratory parameters specified in the protocol.
• Patients who have received neutrophil growth factor support within 14 days of first dose of study drug.
• Patients who require therapy with a concomitant medication that is a strong inhibitor or strong inducer of CYP3A4.
• 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.
• 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.
• Patients who have a history of a seizure disorder requiring anti-seizure medication.

Sponsors & Collaborators

• Blueprint Medicines Corporation: lead

Study Sites (114)

Mayo Clinic Cancer Center

Phoenix, Arizona, 85054, United States

Location

UCLA Hematology/Oncology - Santa Monica

Santa Monica, California, 90404, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Rocky Mountain Cancer Centers

Boulder, Colorado, 80303, United States

Location

Washington Hospital Center - Oncology and Hematology

Washington D.C., District of Columbia, 20010, United States

Location

Mayo Clinic Cancer Center

Jacksonville, Florida, 32224, United States

Location

University of Miami

Miami, Florida, 33146, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Northside Hospital

Atlanta, Georgia, 30341, United States

Location

Northwestern Medicine

Chicago, Illinois, 60611, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

Washington University in Saint Louis

St Louis, Missouri, 63130, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

OHSU - Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

USO - Texas Oncology

Dallas, Texas, 75246, United States

Location

Texas Oncology - Denton South

Denton, Texas, 76210, United States

Location

University of Texas MD Anderson

Houston, Texas, 77030, United States

Location

Texas Oncology - Waco

Waco, Texas, 76712, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Summit Cancer Centers

Spokane, Washington, 99216, United States

Location

Medical College of Wisconsin - Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Flinders Medical Center

Adelaide, Australia

Location

Monash Health

Clayton, Australia

Location

The Canberra Hospital

Garran, Australia

Location

AKH, Klinik f. Innere Med. I, Onkologie

Vienna, Austria

Location

Institut Jules Bordet

Brussels, Belgium

Location

Leuven Cancer Institute

Leuven, Belgium

Location

Cross Cancer Institute

Edmonton, Alberta, Canada

Location

University Health Network

Toronto, Ontario, M5G 1L7, Canada

Location

Jewish General Hospital

Montreal, Canada

Location

Beijing Cancer Hospital

Beijing, China

Location

Chinese PLA General Hospital

Beijing, China

Location

West China Hospital Sichuan University

Chengdu, China

Location

The First Affiliated Hospital of Chongqing Medical University

Chongqing, China

Location

Fujian Medical University Union Hospital

Fuzhou, China

Location

The First Affiliated Hospital of Sun Yat-sen University

Guangzhou, China

Location

The Sixth Affiliated Hospital of Sun Yat-Sen University

Guangzhou, China

Location

The First Affiliated Hospital, Zhejiang University

Hangzhou, China

Location

Harbin Medical University Cancer Hospital

Harbin, China

Location

The First Affiliated Hospital of Nanchang Medical University

Nanchang, China

Location

Guangxi Medical University Affiliated Tumor Hospital & Oncology Medical College

Nanning, China

Location

The Affiliated Hospital of Qingdao University

Qingdao, China

Location

Fudan University Shanghai Cancer Center

Shanghai, China

Location

Fudan University Zhongshan Hospital

Shanghai, China

Location

Shanghai Jiaotong University School of Medicine, Renji Hospital

Shanghai, China

Location

Liaoning Cancer Hospital & Institute

Shenyang, China

Location

Tianjin Cancer Hospital

Tianjin, China

Location

Affiliated Cancer Hospital of Xinjiang Medical University

Ürümqi, China

Location

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

Wuhan, China

Location

Onkologická klinika Fakultní nemocnice Olomouc

Olomouc, Czechia

Location

Fackultni Nemocnice v Motole

Prague, Czechia

Location

Institut Bergonié

Bordeaux, France

Location

Centre Oscar Lambret

Lille, France

Location

UNICANCER - Lyon, Centre Léon-Bérard

Lyon, 69008, France

Location

Institute Paoli Calmettes

Marseille, France

Location

La Timone University Hospital

Marseille, France

Location

Institut Curie

Paris, France

Location

Centre Rene Gauducheau

Saint-Herblain, France

Location

Gustave Roussy Cancer Campus

Villejuif, France

Location

HELIOS Klinikum Bad Saarow

Bad Saarow, Germany

Location

HELIOS Klinikum Berlin-Buch

Berlin, Germany

Location

Medizinische Fakultät Carl Gustav Carus

Dresden, Germany

Location

Universitaetsklindum Essen

Essen, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt, Germany

Location

Studienzentrale GbR Lübecker Onkologische Schwerpunktpraxis Dres. med. Uthgenannt

Lübeck, Germany

Location

Rupercht-Karls-Universitaet Heidelberg

Mannheim, Germany

Location

Fovarosi Onkormanyzat Szent Laszlo Korhaz

Budapest, Hungary

Location

Magyar Honvédség Egészségügyi Központ Onkológiai Osztály

Budapest, Hungary

Location

Medical Oncology University Debrecen

Debrecen, Hungary

Location

University of Pécs

Pécs, Hungary

Location

Azienda Ospedaliero Universitaria Sant'Orsola Malpighi

Bologna, Italy

Location

Candiolo Cancer Institute - FPO, IRCCS

Candiolo, Italy

Location

AOUC Azienda Ospedaliero - Universitaria Careggi

Florence, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori Milano

Milan, Italy

Location

Istituto Europeo di Oncologia

Milan, Italy

Location

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

Palermo, Italy

Location

Campus Bio-Medico - Oncology Medica

Roma, Italy

Location

Nederlands Kanker Instituut - Antoni Van Leeuwenhoek Ziekenhuis

Amsterdam, Netherlands

Location

Radboud University Medical Center

Nijmegen, Netherlands

Location

Erasmus Medical Center

Rotterdam, Netherlands

Location

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

Krakow, Poland

Location

Samodzielny Publiczny Zaklad Opieki Zdrowotnej MSWiA z W-MCO

Olsztyn, Poland

Location

Maria Skodowska Curie Memorial Cancer Centre and Institute of Oncology

Warsaw, Poland

Location

Dolnoslaskie Centrum Onkologii we Wrocawiu

Wroclaw, Poland

Location

National Cancer Centre Singapore

Singapore, Singapore

Location

Ajou University Hospital

Suwon, Gyeong Gi-do, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Severance Hospital

Seoul, South Korea

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Institut Català d'Oncologia - Hospital Duran i Reynals

Barcelona, Spain

Location

Vall d'Hebron

Barcelona, Spain

Location

Hospital La Paz

Madrid, Spain

Location

Hospital Universitario Gregorio Marañón

Madrid, Spain

Location

Hospital Universitario Puerta de Hierro

Madrid, Spain

Location

Hospital Virgen del Rocio

Seville, Spain

Location

Fundacion Instituto Valenciano de Oncologia, Servicio de Oncologia

Valencia, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, Spain

Location

Skanes University Hospital

Lund, Sweden

Location

Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom

Location

The Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

Guy's Hospital

London, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, United Kingdom

Location

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, United Kingdom

Location

Related Publications (3)

• Serrano C, Bauer S, Gomez-Peregrina D, Kang YK, Jones RL, Rutkowski P, Mir O, Heinrich MC, Tap WD, Newberry K, Grassian A, Shi H, Bialick S, Schoffski P, Pantaleo MA, von Mehren M, Trent JC, George S. Circulating tumor DNA analysis of the phase III VOYAGER trial: KIT mutational landscape and outcomes in patients with advanced gastrointestinal stromal tumor treated with avapritinib or regorafenib. Ann Oncol. 2023 Jul;34(7):615-625. doi: 10.1016/j.annonc.2023.04.006. Epub 2023 Apr 25.

  PMID: 37105265 DERIVED

• 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.

  PMID: 34343033 DERIVED

• 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.

  PMID: 30274985 DERIVED

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

avapritinib; regorafenib

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Medical Information Call Center
• Organization: Blueprint Medicines

medinfo@blueprintmedicines.com

1-888-258-7768

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: March 7, 2018
• First Posted: March 14, 2018
• Study Start: March 26, 2018
• Primary Completion: March 9, 2020
• Study Completion: September 15, 2021
• Last Updated: October 6, 2022
• Results First Posted: May 14, 2021

Record last verified: 2022-09

Locations

CZ (2); NL (3); DE (7); PL (4); CN (19); FR (8); ES (9); GB (5); AU (1); IT (7); KR (5); BE (2); US (30); CA (3); SG (1); SE (1); HU (4)