(Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors
(Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors
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.
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.
GIST
Phase III
Adults
Chemotherapy - cytotoxic,
Mol. targeted/Immunotherapy/Biologics
CGT9486 (PLX9486),
SU011248 (Sunitinib),
Sunitinib
Davis, Elizabeth
International
Vanderbilt University
06-23-2022
Eligibility
18 Years
BOTH
NO
Inclusion Criteria:
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:
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
ECOG - 0 to 2
Have clinically acceptable local laboratory screening results (clinical chemistry and hematology) within certain limits
Exclusion Criteria:
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)
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:
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
ECOG - 0 to 2
Have clinically acceptable local laboratory screening results (clinical chemistry and hematology) within certain limits
Exclusion Criteria:
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)
