Title
(PEAK) 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

Description
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.

Objective
Primary: To determine the efficacy of CGT9486+sunitinib vs sunitinib in subjects with GIST

Secondary:
-To evaluate efficacy parameters of CGT9486+sunitinib vs sunitinib in subjects with GIST
-To characterize the safety of CGT9486+sunitinib vs sunitinib in subjects with GIST
-To evaluate additional efficacy parameters of CGT9486+sunitinib vs sunitinib in subjects with GIST
-To evaluate the European Organisation for Research and Treatment of Cancer Quality of Life (EORTCQLQ-C30) scores in subjects with GIST treated with CGT9486+sunitinib vs sunitinib

Exploratory
-To assess disease biomarkers in peripheral blood
-To explore various pharmacodynamic markers and their relationship with clinical safety, efficacy, and PK

Treatment Drug: CGT9486 plus sunitinib
Drug: CGT9486
Drug: Sunitinib
Drug: Sunitinib

Key Eligibility

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

Applicable Disease Sites
Sarcoma

Participating Institutions
UW Health 1 S. Park Medical Center; UW Health Eastpark Medical Center; UW Health University Hospital