(Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorCogent Biosciences, Inc.
About this trial
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).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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)
Documented disease progression on or intolerance to imatinib (Part 1a, Part 1b, Part 2, DDI Substudy)
DDI Substudy/Part 1a: Treatment with ≥1 prior lines of therapy for GIST
Part 1b: Treatment with ≥2 prior TKI for GISTs
Disqualifiers
Known Platelet-Derived Growth Factor Receptor (PDGFR) driving mutations or known succinate dehydrogenase deficiency (Part 1a, Part 1b, Part 2, DDI Substudy)
Clinically significant cardiac disease
Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study drug (Part 1a, Part 1b, Part 2, DDI Substudy)
Gastrointestinal abnormalities including, but not limited to, significant nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption
Trial design
Design model
Parallel
Treatments tested in this trial
CGT9486
DrugParticipants will receive CGT9486 orally until study stopping rules are met.
CGT9486
DrugParticipants will receive CGT9486 until steady state then both CGT9486 and sunitinib orally until study stopping rules are met.
Sunitinib
DrugParticipants will receive sunitinib until steady state then both sunitinib and CGT9486 orally until study stopping rules are met.
Sunitinib
DrugParticipants will receive sunitinib orally until study stopping rules are met.
Midazolam
DrugParticipants will receive a single-dose of midazolam on Day 1 and Day 16
CGT9486
DrugParticipants will receive CGT9486 orally starting on Day 2 until study stopping rules are met.
Sunitinib
DrugParticipants will receive CGT9486 until steady state then both sunitinib and CGT9486 orally until study stopping rules are met.
CGT9486
DrugParticipants will receive sunitinib until steady state then both CGT9486 and sunitinib orally until study stopping rules are met.
Sunitinib
DrugParticipants will receive sunitinib orally starting on Day 16 until study stopping rules are met.
Treatment groups
482 Participants
are divided into 7 treatment groups7
Treatment groupsSee each treatment group below.
Group A: Part 1aExperimental treatment 2 interventions
Group B: Part 2 - Experimental GroupExperimental treatment 2 interventions
Group C: Part 2 - Control GroupActive comparator 1 intervention
Group D: Part 1b - DDI Cohort 1Experimental treatment 2 interventions
Group E: Part 1b - DDI Cohort 2Experimental treatment 2 interventions
Group F: DDI Substudy (Midazolam)Experimental treatment 3 interventions
Group G: GIST 1L SubstudyExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Part 1a - pharmacokinetics - Cmax
Maximum plasma concentration (Cmax)
Time frame
16 days2
Part 1a - pharmacokinetics - AUC
Area under the plasma concentration-time curve (AUC)
Time frame
16 days3
Part 1b - pharmacokinetics - Cmax
Maximum plasma concentration (Cmax)
Time frame
14 days4
Part 1b - pharmacokinetics - AUC
Area under the plasma concentration-time curve (AUC)
Time frame
14 daysSecondary outcomes
1
All Study Parts - observing the safety of each treatment regimen.
Incidence and severity of Adverse Events from first dose of study drug
Time frame
Approximately 48 months2
All Study Parts - observing the safety of each treatment regimen.
Incidence and severity of Serious Adverse Events from first dose of study drug
Time frame
Approximately 48 months3
All Study Parts - observing the safety of each treatment regimen.
Incidence of Adverse Events leading to dose modifications from first dose of study drug
Time frame
Approximately 48 months4
All Study Parts - observing the safety of each treatment regimen.
Change from baseline in laboratory results
Time frame
Approximately 48 monthsSponsors and contacts
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Source ClinicalTrials.gov