PLX9486 as a Single Agent and in Combination With PLX3397 or PLX9486 With Sunitinib in Patients With Advanced Solid Tumors

PLX9486 as a Single Agent and in Combination With PLX3397 or PLX9486 With Sunitinib in Patients With Advanced Solid Tumors

Gastrointestinal Stromal Tumor

Completed

1

Start Date 03/01/2015

Age of Trial (yrs) 9.2

Gleevec-resistant

KIT inhibitor + Tumor Associated Macrophage inhibitor

Block KIT + Stimulate the immune system

Specifically GIST plus other cancers

PLX121-01

Plexxikon

Oscar Alcantar oalcantar@plexxikon.com

Oral

GIST patients will be allowed to join all arms of the trial. Phase 1 is a dose escalation study of the c-Kit inhibitor PLX4986 as a single agent.

PLX3397 is a CSF-1R inhbitor. It blocks the growth of Macrophages in the tumor micro-environment. Macrophage activity has been identified as an adaptive immune system response in GIST. Inhibiting macrophage development may improve GIST cell apoptosis (death).

Description of Arms seems to allow both newly diagnosed unresectable GIST (Arms 1 and 2b) and also Advanced GIST that as failed standard therapies (Arms 2a and 2c).

Purpose: The goal of this clinical research study is to learn how PLX9486 may affect cancer cells with certain mutations in the KIT gene, specifically in patients with types of advanced solid tumors including Gastrointestinal Stromal Tumor (GIST).

PLX9486 is designed to block KIT gene mutations. These mutations can cause cancer and cancer cell growth. By blocking these mutations, the drug may kill the cancer cells with the mutation and/or stop the tumor from growing. By combining PLX9486 with PLX3397, the investigators hope to block most gene mutations in KIT.

Official Title: A Phase 1b Study to Assess Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of PLX9486 as a Single Agent and in Combination With PLX3397 in Patients With Advanced Solid Tumors and Patients With Locally Advanced, Unresectable, or Metastatic Gastrointestinal Stromal Tumor (GIST) Who Have Been Previously Treated With Imatinib Mesylate, Sunitinib Malate, and Regorafenib