Epacadostat and Pembrolizumab in Patients With GIST Epacadostat and Pembrolizumab in Patients With GIST

Epacadostat and Pembrolizumab in Patients With GIST Epacadostat and Pembrolizumab in Patients With GIST

Gastrointestinal Stromal Tumor

Active, not recruiting

2

Start Date 01/01/2018

Age of Trial (yrs) 6.3

Gleevec-resistant

PD-1 + IDO1 inhibitor

Immune checkpoint inhibition

Specifically GIST and only GIST

AAAR1581

Richard D. Carvajal

Richard D Carvajal, MD 646-317-6041 carvajalr@columbia.edu

Oral Intravenous

Breif Summary:
Primary objective is to assess the efficacy of combined IDO and PD-1 inhibition in a single arm phase II trial of epacadostat and pembrolizumab in patients with advanced imatinib-refractory GIST, using a primary endpoint of overall response rate.

Secondary objectives are to evaluate the progression free survival (PFS), the overall survival (OS), the response rate and to evaluate the safety and tolerability of combined epacadostat and pembrolizumab treatment.

The investigator hypothesizes that treatment with epacadostat and pembrolizumab will increase the response rate compared to what has been historically achieved with salvage tyrosine kinase inhibitors.

Detailed Description:
While targeted therapy with imatinib has significantly improved survival for patients with inoperable and metastatic gastrointestinal stromal tumors (GIST), the majority will eventually progress after a median of 20-26 months. Standard second-line treatment with sunitinib has a response rate of 7%, and third-line treatment with regorafenib has a response rate of only 5%. More effective treatments for imatinib-refractory GIST are needed.

This study aims to assess the efficacy of combined IDO and PD-1 inhibition with epacadostat (IDO inhibitor) and pembrolizumab (anti-PD-1 antibody) in patients with imatinib-refractory GIST.

Inclusion Criteria:
Histologically confirmed diagnosis of GIST.
Unresectable or metastatic GIST
Allowable prior therapies:
Subjects must have had clinical or radiographic progression on imatinib. Those who were taken off of imatinib for intolerance must have progressed on at least one other TKI.
Subjects must have received ≥ 1 prior systemic therapy (including imatinib). A maximum of 4 prior therapies for metastatic disease are allowed.