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TERMINATEDPHASE2

Epacadostat and Pembrolizumab in Patients With GIST

A Phase II Study of Epacadostat and Pembrolizumab in Patients With Imatinib Refractory Advanced Gastrointestinal Stromal Tumors

NCT03291054•Columbia University

View on ClinicalTrials.gov

Summary

Primary objective is to assess the efficacy of combined Indoleamine 2,3-dioxygenase (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.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Histologically confirmed diagnosis of GIST.
•Unresectable or metastatic GIST
•Allowable prior therapies:
•1. 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 tyrosine kinase inhibitor (TKI).
•2. Subjects must have received ≥ 1 prior systemic therapy (including imatinib). A maximum of 4 prior therapies for metastatic disease are allowed.
•Male or female subjects, age 18 years or older.
•Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
•Life expectance of ≥ 3 months.
•Laboratory and medical history parameters within the following Protocol-defined range.
•All screening laboratory tests should be performed within 28 days of treatment initiation and must be independent of hematopoietic growth factor support.
+14 more criteria

Exclusion Criteria

•Treatment with chemotherapy (not including Tyrosine Kinase Inhibitors) or radiotherapy within 4 weeks (6 weeks from nitrosoureas or mitomycin C), or treatment with monoclonal antibody therapy within 4 weeks prior to start of study treatment. Note: No minimum washout period is required for tyrosine kinase inhibitor therapy (eg, imatinib or sunitinib).
•Patients must have recovered from adverse events (greater than grade 1) due to prior anticancer therapy, except for stable chronic toxicities such as alopecia.
•Participation in any other clinical study with investigational drug received within 28 days or 5 half lives (whichever is longer) before first dose.
•Subjects who have received prior anti-PD-1 or anti-PD-L1 antibody, or an IDO inhibitor.
•Subjects who have received experimental vaccines or other immune therapies should be discussed with the principal investigator to confirm eligibility.
•Any prior ≥ Grade 3 immune-related adverse event (irAE) while receiving immunotherapy, or any unresolved irAE \> grade 1.
•Subjects receiving immunologically based treatment for any reason, including chronic steroids or prednisone (at dose \>10 mg/day of prednisone) within 14 day prior to first study treatment. Inhaled or topical steroids or systemic steroids (at dose ≤10 mg/day of prednisone) is permitted.
•Subjects with any active or inactive autoimmune process (eg, rheumatoid arthritis, moderate or severe psoriasis, multiple sclerosis, inflammatory bowel disease) or who are receiving systemic therapy for an autoimmune disease. Exceptions include vitiligo, hypothyroidism controlled on hormone replacement, type I diabetes, Grave's disease, adrenal insufficiency on stable replacement doses of steroids (prednisone ≤10 mg/day or equivalent), or with principal investigator approval.
•No prior organ allograft or allogenic bone marrow transplantation.
•History of (noninfectious) pneumonitis that require steroids or current pneumonitis.
+15 more criteria

Locations (2)

U-M Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Columbia University Irving Medical Center

New York, New York, United States

Key Dates

Start Date

February 28, 2018

Primary Completion Date

August 19, 2020

Completion Date

August 19, 2020

Last Updated

June 11, 2024

Enrollment

ACTUAL participants

Conditions

Gastrointestinal Stromal Tumors

Interventions

Pembrolizumab

DRUG

Epacadostat

DRUG

The Correlation Between Ripretinib Exposure and the Efficacy and Safety in Patients with Advanced GISTs

NCT06431451

Gastrointestinal Stromal Tumors

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RECRUITING

Second-line Pharmacotherapy Patterns and Outcomes of Advanced Gastrointestinal Stromal Tumor: A Real-world Study

NCT05440357

Gastrointestinal Stromal Tumors

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RECRUITING

A Cohort Study on the Safety of Laparoscopic Resection of 5cm or Larger Gastric Gastrointestinal Stromal Tumors

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: June 11, 2024Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Epacadostat and Pembrolizumab in Patients With GIST

Inclusion Criteria

Exclusion Criteria

The Correlation Between Ripretinib Exposure and the Efficacy and Safety in Patients with Advanced GISTs

Second-line Pharmacotherapy Patterns and Outcomes of Advanced Gastrointestinal Stromal Tumor: A Real-world Study

A Cohort Study on the Safety of Laparoscopic Resection of 5cm or Larger Gastric Gastrointestinal Stromal Tumors

Clinical Research of Drug Holiday Based on MRD Detection in GIST Patients at High Risk of Recurrence

Apatinib Mesylate Versus Standard Second-line TKI in the Treatment of Advanced GIST

SARC044: A Phase II Trial of Bezuclastinib in Combination With Sunitinib in Patients With GIST