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b'Written informed consent' |
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b'At least 20 years old in Japan or 18 years old in other countries at the time of' |
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b'ignature of the informed consent form (ICF), following local regulatory requirements' |
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b'Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1' |
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b'Has histopathologically documented unresectable and/or metastatic GIST meeting the' |
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b'criteria below:' |
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b'Dose Escalation (Part 1): Participants should meet one of the following criteria:' |
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b'(For US sites only) Participants with GIST who have progressed on or are' |
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b'intolerant to imatinib (IM) and at least one post-IM treatment or who are not' |
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b'candidates for post-IM standard of care treatment' |
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b'(For Japan sites only) Participants with GIST who have received all the existing' |
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b'tandard of care treatments or who are not candidates for one or more available' |
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b'post-IM standard of care treatments' |
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b'Participants with GIST who are not candidates for IM or curative intent surgical' |
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b'treatment (i.e., participants without activating KIT or platelet-derived growth' |
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b'factor receptor alpha (PDGFRa) mutations, with PDGFRa D842V mutations, or are KIT' |
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b'negative by local results)' |
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b'Dose Expansion (Part 2) Cohort 1: Participants with GIST who have progressed on or are' |
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b'intolerant to IM and at least one post-IM treatment' |
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b'Dose Expansion (Part 2) Cohort 2: Participants with GIST who have progressed on IM and' |
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b'had not received a post-IM treatment (2nd line)' |
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b'Consents to provide fresh tumor biopsy tissue samples both before and on DS-6157a' |
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b'treatment for the measurement of GPR20 levels by immunohistochemistry and other' |
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b'biomarkers' |
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b'Has a left ventricular ejection fraction (LVEF) \\u226550% by either echocardiogram (ECHO)' |
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b'or multi-gated acquisition scan (MUGA) within 28 days before study treatment' |
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b'Has at least 1 measurable lesion based on RECIST Version 1.1 as assessed by the' |
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b'Investigator' |
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b'Has adequate organ function within 7 days before the start of study treatment, defined' |
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b'as:' |
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b'Platelet count \\u2265100,000/mm^3' |
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b'Hemoglobin \\u22658.5 g/dL' |
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b'Absolute neutrophil count \\u22651,500/mm^3' |
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b'Creatinine clearance \\u226550 mL/min' |
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b'Aspartate aminotransferase \\u22643 \\xd7 upper limit of normal (ULN) (if liver metastases' |
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b'are present, \\u22645 \\xd7 ULN)' |
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b'Alanine aminotransferase \\u22643 \\xd7 ULN (if liver metastases are present, \\u22645 \\xd7 ULN)' |
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b'Total bilirubin \\u22641.5 \\xd7 ULN or \\u22643.0 \\xd7 ULN for participants with documented history' |
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b"of Gilbert's Syndrome" |
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b'Has an adequate treatment washout period prior to start of study treatment, defined' |
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b'as:' |
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b'Major surgery: \\u22654 weeks (or 2 weeks for minor surgeries)' |
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b'Radiation therapy: \\u22653 weeks (or 2 weeks for palliative radiation excluding pelvic' |
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b'radiation)' |
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b'Systemic anti-cancer therapy (except for anti-androgen for prostate cancer and' |
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b'bisphosphonate, denosumab, or medroxyprogesterone acetate for bone metastases):' |
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b'Cytotoxic chemotherapy: \\u22653 weeks or 5 times the terminal elimination' |
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b'half-life (t\\xbd) of the chemotherapeutic agent, whichever is shorter' |
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b'Antibody and antibody-conjugates therapy: \\u22653 weeks or 5 times the t\\xbd,' |
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b'whichever is longer' |
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b'Prior tyrosine kinase inhibitors (TKIs): washout period from 2 to 21 days' |
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b'depending on the TKI' |
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b'Immunotherapy: \\u22654 weeks.' |
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b'Male participants with female partners of childbearing potential and female' |
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b'participants of child-bearing potential must agree to use a highly effective form of' |
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b'contraception, or avoid intercourse during and upon completion of the study and for at' |
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b'least 4 months (for males) and for at least 7 months (for females) after the last dose' |
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b'of study drug.' |
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b'History of an allogeneic bone marrow or solid organ transplant within 3 months before'
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b'the start of study treatment'
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b'Concomitant treatment with any medication that is classified as having a known risk of'
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b'Torsades de pointes should be avoided from the start of study treatment through the'
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b'end of Cycle 3'
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b'Prophylactic administration of granulocyte colony-stimulating factor (G-CSF),'
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b'filgrastim, pegfilgrastim, erythropoietin, or the transfusion of blood, red blood'
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b'cells, or platelets within 14 days before the start of treatment and during Cycle 1.'
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b'Chronic therapy with erythropoietin at stable dose that started at least 14 days'
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b'before the first dose of DS-6157a may continue.'
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b'Has unresolved toxicities from previous anticancer therapy, defined as toxicities'
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b'(other than alopecia) not yet resolved to National Cancer Institute Common Terminology'
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b'Criteria for Adverse Events version 5.0, Grade \\u22641. Participants with chronic Grade 2'
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b'toxicities may be eligible.'
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b'Has spinal cord compression or clinically active central nervous system (CNS)'
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b'metastases (including brain metastases), defined as untreated and symptomatic, or'
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b'requiring therapy with steroids or anticonvulsants to control associated symptoms'
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b'Has known hypersensitivity to either the drug substances or inactive ingredients in'
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b'the drug product'
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b'Has a prior or concurrent malignancy whose natural history or treatment has the'
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b'potential to interfere with the safety, efficacy, or any other assessments of the'
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b'investigational regimen'
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b'Has a documented history of myocardial infarction or unstable angina within 6 months'
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b'before study treatment'
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b'Has a medical history of symptomatic congestive heart failure (New York Heart'
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b'Association classes II-IV) or a serious cardiac arrhythmia requiring treatment'
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b"Has a corrected QT by Fridericia's formula (QTcF), of >470 ms based on the average of"
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b'triplicate 12-lead electrocardiogram (ECG) per local read'
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b'Has a documented history of (non-infectious) interstitial lung disease'
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b'(ILD)/pneumonitis that required corticosteroids, has current ILD/pneumonitis, or where'
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b'uspected ILD/pneumonitis cannot be ruled out by imaging at screening'
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b'Has clinically significant pulmonary compromise or requirement for supplemental oxygen'
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b'Has clinically significant corneal disease'
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b'Has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals'
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b'Has active human immunodeficiency virus (HIV) infection as determined by plasma HIV'
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b'RNA viral load.'
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b'Has evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection,'
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b'as manifest by the detectable viral load (HBV-DNA or HCV-RNA, respectively)'
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b'Is a lactating mother (women who are willing to temporarily interrupt breastfeeding'
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b'will also be excluded), or pregnant as confirmed by pregnancy tests performed within 7'
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b'days before study treatment'
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b'Women who plan to become pregnant while in the study and for at least 7 months after'
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b'the last administration of study treatment'
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b'Men who plan to father a child while in the study and for at least 4 months after the'
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b'last administration of study treatment'
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b'Any evidence of severe or uncontrolled systemic diseases, including uncontrolled'
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b'hypertension, uncontrolled diabetes mellitus, active bleeding diatheses, substance'
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b'abuse, or other medical condition that would increase the risk of toxicity or'
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b'interfere with participation of the participant or evaluation of the clinical study'
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