(Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors
- Conditions
- Advanced Gastrointestinal Stromal TumorsMetastatic Cancer
- Interventions
- Registration Number
- NCT05208047
- Lead Sponsor
- Cogent Biosciences, Inc.
- Brief Summary
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 442 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 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. Additionally, a drug-drug interactions substudy will investigate the potential for CGT9486 to be a CYP3A4 inducer in approximately 16 patients who have received at least one prior line of therapy for GIST.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 442
-
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.
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Documented disease progression on or intolerance to imatinib
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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
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Have at least 1 measurable lesion according to mRECIST v1.1 (Part1a, Part 1b, Part 2)
-
ECOG - 0 to 2
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Have clinically acceptable local laboratory screening results (clinical chemistry and hematology) within certain limits
Key
- Known PDGFR driving mutations or known succinate dehydrogenase deficiency
- Clinically significant cardiac disease
- Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study drug
- Gastrointestinal abnormalities including, but not limited to, significant nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption
- Any active bleeding excluding hemorrhoidal or gum bleeding
- Seropositive for HIV 1 or 2, or positive for hepatitis B surface antigen or hepatitis C virus (HCV) antibody.
- Active, uncontrolled, systemic bacterial, fungal, or viral infections at Screening
- Received strong CYP3A4 inhibitors or inducers
- Received sunitinib within 3 weeks (Part 1a, Part 1b, DDI Substudy)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1a CGT9486 plus sunitinib CGT9486 plus sunitinib 37.5 mg QD Part 2 - Experimental Group CGT9486 plus sunitinib CGT9486 plus sunitinib 37.5 mg QD Part 2 - Control Group Sunitinib sunitinib 37.5 mg QD Part 1b - DDI Cohort 1 CGT9486 CGT9486 plus sunitinib 37.5 mg QD Part 1b - DDI Cohort 2 Sunitinib sunitinib 37.5 mg QD plus CGT9486 DDI Substudy (Midazolam) Midazolam Midazolam, CGT9486, sunitinib DDI Substudy (Midazolam) CGT9486 plus sunitinib Midazolam, CGT9486, sunitinib
- Primary Outcome Measures
Name Time Method Part 1b - pharmacokinetics - AUC 14 days Area under the plasma concentration-time curve (AUC)
Part 1b - pharmacokinetics - Tmax 14 days Time to maximum observed plasma concentration (Tmax)
Part 2 - Progression Free Survival (PFS) Approximately 48 months Time from first dose to documented disease progression or death due to any cause, whichever occurs first
DDI Substudy - pharmacokinetics - AUC 16 days Area under the plasma concentration-time curve (AUC)
DDI Substudy - pharmacokinetics - Cmax 14 days Maximum plasma concentration (Cmax)
Part 1a - pharmacokinetics - Cmax 16 days Maximum plasma concentration (Cmax)
Part 1a - pharmacokinetics - AUC 16 days Area under the plasma concentration-time curve (AUC)
Part 1b - pharmacokinetics - Cmax 14 days Maximum plasma concentration (Cmax)
- Secondary Outcome Measures
Name Time Method All Study Parts - observing the safety of each treatment regimen. Approximately 48 months Change from baseline in laboratory results
Part 1a, Part 1b, Part 2 - Overall Survival (OS) Approximately 48 months Time from first dose to death due to any cause
Part 1a, Part 1b, Part 2 - Objective Response Rate (ORR) Approximately 48 months Percentage of subjects who achieved documented complete response (CR) + confirmed partial response (PR) based on modified Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Part 1a, Part 1b, Part 2 - Disease Control Rate (DCR) Approximately 48 months Percentage of subjects who achieved CR + PR + stable disease (SD) at 16 weeks
Part 1a, Part 1b. Part 2 - Time to response (TTR) Approximately 48 months Time from first dose to first documented response based on modified Response Evaluation Criteria in Solid Tumors Version 1.1
Part 1a, Part 1b, Part 2 - Duration of Response (DOR) Approximately 48 months Time from first response (CR or PR) to the date of progression or death from any cause, whichever occurs first
Part 2 Only - European Organisation for Research and Treatment of Cancer Quality of Life (EORTC-QLQ-30) Approximately 48 months Change in individual scores in patients with locally advanced, unresectable, or metastatic GIST treated with CGT9486 in combination with sunitinib compared with patients treated with sunitinib monotherapy. The scale comprises 30 questions, 24 of which are aggregated into 9 multi-item scales, to include 5 functioning scales (physical, role, cognitive, emotional and social), 3 symptom scales (fatigue, pain and nausea/vomiting) and 1 global health status scale. The remaining 6 single-item scales assess symptoms (dyspnea, appetite loss, sleep disturbance, constipation, diarrhea and the financial impact). All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning, while higher scores on the symptom and single-item scales indicate a higher level of symptoms.
Trial Locations
- Locations (125)
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
University of Arizona- Cancer Center
🇺🇸Tucson, Arizona, United States
City of Hope
🇺🇸Duarte, California, United States
University of California, Los Angeles (UCLA)
🇺🇸Los Angeles, California, United States
University of California, San Diego (UCSD)
🇺🇸San Diego, California, United States
University of California, San Francisco
🇺🇸San Francisco, California, United States
University of Colorado Denver
🇺🇸Denver, Colorado, United States
MedStar Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
Mayo Clinic Jacksonville
🇺🇸Jacksonville, Florida, United States
Scroll for more (115 remaining)University of Alabama at Birmingham🇺🇸Birmingham, Alabama, United States