Clinical Trial 23228

• Overview

  Study Title:

  An International, Phase 3, Randomized, Multicenter, Open-label Study of Ripretinib vs Sunitinib in Patients with Advanced Gastrointestinal Stromal Tumor (GIST) with KIT Exon 11 and Co-occurring KIT Exons 17 and/or 18 Mutations Who Were Previously Treated with Imatinib (INSIGHT)

  Summary:

  This is a Phase 3, 2-arm, randomized, open-label, global, multicenter study comparing the efficacy of ripretinib to sunitinib in participants with Gastrointestinal Stromal Tumors(GIST) who progressed on first-line treatment with imatinib, harbor co-occurring KIT exons 11+17/18 mutations, and are without KIT exon 9, 13, or 14 mutations.

  Objective:

  Primary Objective: * To compare the efficacy of ripretinib vs sunitinib as measured by progression-free survival (PFS) based on independent radiologic review (IRR) Secondary Objectives: * To compare the objective response rate (ORR) by IRR of ripretinib vs sunitinib using modified Response Evaluation Criteria in Solid Tumors v1.1 GIST-specific (mRECIST) * To compare the overall survival (OS) of ripretinib vs sunitinib * To compare quality of life (QoL) during treatment as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer 30-item (EORTC-QLQ-C30), select items from the National Cancer Institute Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (NCI-PRO-CTCAE), and the EuroQol 5‑Dimension 5‑Level (EQ-5D-5L) of ripretinib vs sunitinib * To compare disease control rate (DCR) by IRR, time-to-progression (TTP) by IRR, PFS based on Investigator assessment, duration of response (DOR) by IRR, and time-to response (TTR) by IRR of ripretinib vs sunitinib * To assess progression-free survival 2 (PFS2) and second PFS by Investigator assessment * To assess the safety profiles of ripretinib vs sunitinib

• Treatments

  Therapies:

  Therapy (NOS)

  Medications:

  DCC-2618 (Ripretinib); Ripretinib (); Sunitinib ()

• Inclusion Criteria

  Inclusion Criteria:
  • Male or female 18 years of age or older.
  • Histologic diagnosis of GIST with co-occurring KIT exons 11+17/18 mutations confirmed by ctDNA sample.
  • Participants must have advanced GIST and radiologic progression on imatinib treatment.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 or less at screening.
  • Female participants of childbearing potential must have a negative pregnancy test at screening and prior to the first dose of study drug.
  • Participants of reproductive potential must agree to follow contraception requirements.
  • Participants must have at least 1 measurable lesion according to mRECIST v1.1 within 21 days prior to the first dose of study drug.
  • Adequate organ function and bone marrow reserve based on laboratory assessments performed at screening.
  • Resolution of all toxicities from prior therapy to Grade 1 or less (or participant baseline) within 1 week prior to the first dose of study drug.

• Exclusion Criteria

  Exclusion Criteria:
  • History of KIT exon 9 mutation or detection of KIT exon 9, 13, or 14 mutations in a ctDNA sample.
  • Has known active central nervous system metastases.
  • New York Heart Association Class II-IV heart disease, myocardial infarction within 6 months of Cycle 1 Day 1, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension, or congestive heart failure.
  • Use of strong or moderate inhibitors or inducers of cytochrome P450 (CYP) 3A prior to the first dose of study drug, and consumption of grapefruit or grapefruit juice within 14 days prior to the first dose of study drug.
  • Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study drug.
  • Known human immunodeficiency virus or hepatitis C infection only if the participant is taking medications that are excluded per protocol, acute or chronic hepatitis B, or acute or chronic hepatitis C infection.
  • Gastrointestinal abnormalities including, but not limited to: inability to take oral medication, malabsorption syndromes, requirement for intravenous alimentation
  • Any active bleeding excluding hemorrhoidal or gum bleeding.

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