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NCT03465722 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2022-10-06

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

Overall Survival (OS) in Patients With Advanced GIST Treated With Avapritinib Compared to Patients Treated With Regorafenib

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outcome · POSTED

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

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility 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.
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    300 mg PO QD
    intervention Names
    1. Drug: avapritinib
    label
    avapritinib
    type
    EXPERIMENTAL
  2. description
    160 mg PO QD
    intervention Names
    1. Drug: regorafenib
    label
    regorafenib
    type
    ACTIVE_COMPARATOR
interventions
  1. arm Group Labels
    1. avapritinib
    description
    Avapritinib tablets for oral administration. Avapritinib will be dosed at 300 mg once daily, continuously.
    name
    avapritinib
    other Names
    1. BLU-285
    type
    DRUG
  2. arm Group Labels
    1. regorafenib
    description
    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).
    name
    regorafenib
    other Names
    1. Stivarga
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
476
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    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.
    measure
    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
secondary Outcomes
  1. description
    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
    measure
    Objective Response Rate (ORR) Determined by Central Radiology Assessment Per mRECIST, Version 1.1
    time Frame
    24 Months
  2. description
    To evaluate overall survival (OS) in patients with advanced GIST treated with avapritinib compared to patients treated with regorafenib
    measure
    Overall Survival (OS) in Patients With Advanced GIST Treated With Avapritinib Compared to Patients Treated With Regorafenib
    time Frame
    24 Months
  3. description
    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.
    measure
    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
Full 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.
Source references
references
  1. citation
    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
    type
    DERIVED
  2. citation
    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
    type
    DERIVED
  3. citation
    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
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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        tients who did not respond to imatinib and at least one additional TKI):</p> <div class="pdq-content-list"><ol id="_422"><li><a href="/clinicaltrials/NCT03465722">VOYAGER</a> (NCT03465722) was a phase III open-label trial of 476 patients with advanced GISTs that did not respond to imatinib and at least one additional TK
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        to imatinib and at least one additional TKI):</p> <div class="pdq-content-list"><ol id="_422"><li><a href="/clinicaltrials/NCT03465722">VOYAGER</a> (NCT03465722) was a phase III open-label trial of 476 patients with advanced GISTs that did not respond to imatinib and at least one additional TKI. Patients were randomly
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      1. context
        Updated: December 13, 2024
        datetime
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        display
        December 13, 2024

    Preserved source evidence · Not medical advice