(Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors
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 482 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 Gastrointestinal Stromal Tumors (GIST) and 2) evaluating the potential 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. This study also contains two substudies: 1) a drug-drug interactions (DDI) substudy will investigate the potential for CGT9486 to be a Cytochrome P450 (CYP)3A4 inducer in approximately 16 patients who have received at least one prior line of therapy for GIST and 2) a substudy intended to test the efficacy of bezuclastinib and sunitinib as first-line (1L) treatment of GIST in approximately 40 participants with KIT exon 9 mutations and no prior systemic therapy (with the exception of up to 10 subjects with ongoing imatinib therapy of ≤4 weeks).
Conditions
- Advanced Gastrointestinal Stromal Tumors
- Metastatic Cancer
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 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. (GIST 1L Substudy: must have documented mutation in KIT Exon 9 with an available molecular pathology report; archival or fresh tumor tissue sample will be required) 2. Documented disease progression on or intolerance to imatinib (Part 1a, Part 1b, Part 2, DDI Substudy) 3. Subjects must have received the following treatment: - DDI Substudy/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 - GIST 1L Substudy: No prior systemic therapy for GIST including adjuvant therapy. Exception: up to 10 subjects with ongoing imatinib therapy of ≤4 weeks 4. Have at least 1 measurable lesion according to mRECIST v1.1 (Part1a, Part 1b, Part 2, GIST 1L Substudy) 5. Eastern Cooperative Oncology Group (ECOG) Status - 0 to 2 (Part 1a, Part 1b, Part 2, DDI Substudy) - 0 to 1 (GIST 1L Substudy) 6. Have clinically acceptable local laboratory screening results (clinical chemistry and hematology) within certain limits
Exclusion Criteria
- Known Platelet-Derived Growth Factor Receptor (PDGFR) driving mutations or known succinate dehydrogenase deficiency (Part 1a, Part 1b, Part 2, DDI Substudy) 2. Clinically significant cardiac disease 3. Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study drug (Part 1a, Part 1b, Part 2, DDI Substudy) 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 (Part 1a, Part 1b, Part 2, DDI Substudy) 9. Received sunitinib within 3 weeks (Part 1a, Part 1b, DDI Substudy)
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. The DDI substudy is a single-arm, fixed-sequence, crossover design to investigate the potential for CGT9486 to be a CYP3A4 inducer. The GIST 1L substudy is a single-arm study of bezuclastinib+sunitinib exploring efficacy in a 1L setting.
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Part 1a |
CGT9486 plus sunitinib 37.5 mg QD |
|
|
Experimental Part 2 - Experimental Group |
CGT9486 plus sunitinib 37.5 mg QD |
|
|
Active Comparator Part 2 - Control Group |
sunitinib 37.5 mg QD |
|
|
Experimental Part 1b - DDI Cohort 1 |
CGT9486 plus sunitinib 37.5 mg QD |
|
|
Experimental Part 1b - DDI Cohort 2 |
sunitinib 37.5 mg QD plus CGT9486 |
|
|
Experimental DDI Substudy (Midazolam) |
Midazolam, CGT9486, sunitinib |
|
|
Experimental GIST 1L Substudy |
CGT9486, sunitinib |
|
Recruiting Locations
Washington D.C., District of Columbia 20010
More Details
- Status
- Recruiting
- Sponsor
- Cogent Biosciences, Inc.