(Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors
Study Details
Study Description
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 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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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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.
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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.
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Active Comparator: Part 2 - Control Group sunitinib 37.5 mg QD |
Drug: Sunitinib
Participants will receive sunitinib orally until study stopping rules are met.
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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.
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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.
|
Outcome Measures
Primary Outcome Measures
- 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)
- 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
Secondary Outcome Measures
- All Study Parts - observing the safety of each treatment regimen. [Approximately 48 months]
Incidence and severity of Adverse Events from first dose of study drug
- All Study Parts - observing the safety of each treatment regimen. [Approximately 48 months]
Incidence and severity of Serious Adverse Events from first dose of study drug
- All Study Parts - observing the safety of each treatment regimen. [Approximately 48 months]
Incidence of Adverse Events leading to dose modifications from first dose of study drug
- All Study Parts - observing the safety of each treatment regimen. [Approximately 48 months]
Change from baseline in laboratory results
- All Study Parts - Overall Survival (OS) [Approximately 48 months]
Time from first dose to death due to any cause
- All Study Parts - 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
- All Study Parts - Disease Control Rate (DCR) [Approximately 48 months]
Percentage of subjects who achieved CR + PR + stable disease (SD) at 16 weeks
- All Study Parts - 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
- All Study Parts - 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.
Eligibility Criteria
Criteria
Key Inclusion Criteria:
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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:
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Part 1a: Treatment with ≥1 prior lines of therapy for GIST
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Part 1b: Treatment with ≥2 prior TKI for GISTs
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Part 2: Prior treatment with imatinib only
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Have at least 1 measurable lesion according to mRECIST v1.1
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ECOG - 0 to 2
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Have clinically acceptable local laboratory screening results (clinical chemistry and hematology) within certain limits
Key Exclusion Criteria:
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Known PDGFR driving mutations or known succinate dehydrogenase deficiency
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Clinically significant cardiac disease
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Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study drug
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Gastrointestinal abnormalities including, but not limited to, significant nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption
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Any active bleeding excluding hemorrhoidal or gum bleeding
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Seropositive for HIV 1 or 2, or positive for hepatitis B surface antigen or hepatitis C virus (HCV) antibody.
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Active, uncontrolled, systemic bacterial, fungal, or viral infections at Screening
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Received strong CYP3A4 inhibitors or inducers
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Received sunitinib within 3 weeks (Part 1a, Part 1b)
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | City of Hope | Duarte | California | United States | 91010 |
2 | MedStar Washington Hospital Center | Washington | District of Columbia | United States | 20010 |
3 | University of Miami - Sylvester Comprehensive Cancer Center | Miami | Florida | United States | 33136 |
4 | Mid Florida Hematology and Oncology Center | Orange City | Florida | United States | 32763 |
5 | Orlando Health Cancer Institute | Orlando | Florida | United States | 32806 |
6 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02115 |
7 | University of Michigan Comprehensive Cancer Center | Ann Arbor | Michigan | United States | 48109 |
8 | Washington University | Saint Louis | Missouri | United States | 63130 |
9 | University of Toledo Medical Center | Toledo | Ohio | United States | 43614 |
10 | Fox Chase Cancer Center | Philadelphia | Pennsylvania | United States | 19111 |
11 | Vanderbilt University Medical Center | Nashville | Tennessee | United States | 37232 |
12 | The University of Texas MD Anderson Cancer Center | Houston | Texas | United States | 77030-4009 |
Sponsors and Collaborators
- Cogent Biosciences, Inc.
Investigators
- Study Director: Jessica Sachs, MD, Cogent Biosciences
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CGT9486-21-301