Purpose

This is a Phase 3, open-label, international, multicenter study of CGT9486 in combination with sunitinib. This is a multi-part study that will enroll approximately 426 patients. Part 1 consists of two evaluations: 1) confirming the dose of an updated formulation of CGT9486 to be used in subsequent parts in approximately 20 patients who have received at least one prior line of therapy for GIST and 2) evaluating for drug-drug interactions between CGT9486 and sunitinib in approximately 18 patients who have received at least two prior tyrosine kinase inhibitors (TKIs) for GISTs. The second part of the study will enroll approximately 388 patients who are intolerant to, or who failed prior treatment with imatinib only and will compare the efficacy of CGT9486 plus sunitinib to sunitinib alone with patients being randomized in a 1:1 manner.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Histologically confirmed locally advanced, metastatic, and/or unresectable GIST. Molecular pathology report must be available for Part 2; if molecular pathology report is unavailable or inadequate, an archival or fresh tumor tissue sample will be required to evaluate mutational status prior to randomization. 2. Documented disease progression on or intolerance to imatinib 3. Subjects must have received the following treatment: - Part 1a: Treatment with ≥1 prior lines of therapy for GIST - Part 1b: Treatment with ≥2 prior TKI for GISTs - Part 2: Prior treatment with imatinib only 4. Have at least 1 measurable lesion according to mRECIST v1.1 5. ECOG - 0 to 2 6. Have clinically acceptable local laboratory screening results (clinical chemistry and hematology) within certain limits

Exclusion Criteria

  1. Known PDGFR driving mutations or known succinate dehydrogenase deficiency 2. Clinically significant cardiac disease 3. Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study drug 4. Gastrointestinal abnormalities including, but not limited to, significant nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption 5. Any active bleeding excluding hemorrhoidal or gum bleeding 6. Seropositive for HIV 1 or 2, or positive for hepatitis B surface antigen or hepatitis C virus (HCV) antibody. 7. Active, uncontrolled, systemic bacterial, fungal, or viral infections at Screening 8. Received strong CYP3A4 inhibitors or inducers 9. Received sunitinib within 3 weeks (Part 1a, Part 1b)

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
This is a multi-part study: Part 1a is a single-arm design, Part 1b is a two-arm parallel design drug-drug interaction evaluation in the first treatment cycle and single-arm design in subsequent treatment cycles, and Part 2 is a randomized two-arm parallel comparator study
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Part 1a
CGT9486 plus sunitinib 37.5 mg QD
  • Drug: CGT9486 plus sunitinib
    Participants will receive both CGT9486 and sunitinib orally until study stopping rules are met.
Experimental
Part 2 - Experimental Group
CGT9486 plus sunitinib 37.5 mg QD
  • Drug: CGT9486 plus sunitinib
    Participants will receive both CGT9486 and sunitinib orally until study stopping rules are met.
Active Comparator
Part 2 - Control Group
sunitinib 37.5 mg QD
  • Drug: Sunitinib
    Participants will receive sunitinib orally until study stopping rules are met.
    Other names:
    • sunitinib - Part 2
Experimental
Part 1b - DDI Cohort 1
CGT9486 plus sunitinib 37.5 mg QD
  • Drug: CGT9486
    Participants will receive CGT9486 until steady state then both CGT9486 and sunitinib orally until study stopping rules are met.
Experimental
Part 1b - DDI Cohort 2
sunitinib 37.5 mg QD plus CGT9486
  • Drug: Sunitinib
    Participants will receive sunitinib until steady state then both sunitinib and CGT9486 orally until study stopping rules are met.
    Other names:
    • sunitinib - Part 1b

Recruiting Locations

University of Alabama at Birmingham
Birmingham, Alabama 35249

More Details

Status
Recruiting
Sponsor
Cogent Biosciences, Inc.

Study Contact

Cogent Biosciences
617-945-5576
peakinfo@cogentbio.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.