Resumen

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.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

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.
Documented disease progression on or intolerance to imatinib
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
Have at least 1 measurable lesion according to mRECIST v1.1 (Part1a, Part 1b, Part 2)
ECOG - 0 to 2
Have clinically acceptable local laboratory screening results (clinical chemistry and hematology) within certain limits

Criterios de exclusión

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)

Intervenciones

drug

CGT9486 plus sunitinib

Participants will receive both CGT9486 and sunitinib orally until study stopping rules are met.

drug

CGT9486

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

drug

Sunitinib

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

drug

Sunitinib

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

drug

Midazolam

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

drug

CGT9486 plus sunitinib

Patients will receive CGT9486 orally starting on Day 2 and sunitinib starting on Day 16 until study stopping rules are met.

A Phase 3 Randomized, Open-Label, Multicenter Clinical Study of CGT9486+Sunitinib vs. Sunitinib in Subjects With Locally Advanced, Unresectable, or Metastatic Gastrointestinal Stromal Tumors

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

CGT9486 plus sunitinib

CGT9486

Sunitinib

Sunitinib

Midazolam

CGT9486 plus sunitinib

Ubicaciones

Instituto Alexander Fleming

Instituto Oncologico de Cordoba (IONC)

Patrocinadores