(Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors

Condition(s) studied

Investigational drug(s) / intervention(s)

CGT9486: Participants will receive CGT9486 orally until study stopping rules are met.

CGT9486: Participants will receive CGT9486 until steady state then both CGT9486 and sunitinib orally until study stopping rules are met.

Sunitinib: Participants will receive sunitinib until steady state then both sunitinib and CGT9486 orally until study stopping rules are met.

Sunitinib: Participants will receive sunitinib orally until study stopping rules are met.

Midazolam: Participants will receive a single-dose of midazolam on Day 1 and Day 16

CGT9486: Participants will receive CGT9486 orally starting on Day 2 until study stopping rules are met.

Sunitinib: Participants will receive CGT9486 until steady state then both sunitinib and CGT9486 orally until study stopping rules are met.

CGT9486: Participants will receive sunitinib until steady state then both CGT9486 and sunitinib orally until study stopping rules are met.

Sunitinib: Participants will receive sunitinib orally starting on Day 16 until study stopping rules are met.

Study 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 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

Primary outcome measure(s)

• 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
• DDI Substudy - pharmacokinetics - AUC — 16 days
  Area under the plasma concentration-time curve (AUC)
• DDI Substudy - pharmacokinetics - Cmax — 14 days
  Maximum plasma concentration (Cmax)

Trial sites (126)

+ 86 more sites — see the full list on the official registry below.