Epacadostat and Pembrolizumab in Patients With GIST

NCT03291054 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: AAAR1581
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Gastrointestinal Stromal Tumors

Keywords

Gastrointestinal Stromal Tumors; GIST; Pembrolizumab; Epacadostat; Columbia

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  The primary endpoint is the overall response rate as defined as the best response using RECIST v1.1 criteria. A standard way to measure how well a cancer patient responds to treatment. It is based on whether tumors shrink, stay the same, or get bigger. To use RECIST, there must be at least one tumor that can be measured on x-rays, CT scans, or MRI scans. The types of response a patient can have are a complete response (CR), a partial response (PR), progressive disease (PD), and stable disease (SD). Also called Response Evaluation Criteria In Solid Tumors.

  within the first 24 weeks of the start of study therapy

Secondary Outcomes (1)

• Overall Survival

  time from registration up to 2 years

Study Arms (1)

Epacadostat and pembrolizumab

EXPERIMENTAL

Subjects will receive epacadostat and pembrolizumab

Drug: Pembrolizumab; Drug: Epacadostat

Interventions

Pembrolizumab DRUG

Subjects will receive pembrolizumab 200 mg (flat dose) IV every 3 weeks on day 1 of a 21 day cycle.

Also known as: Keytruda, Anti-PD-1 antibody

Epacadostat and pembrolizumab

Epacadostat DRUG

Epacadostat will be dosed at 100 mg PO twice a day (BID) daily. Doses should be taken twice daily, in the morning and evening, approximately 12 hours apart, without regard to food.Doses will be self-administered, except on Cycle 2 Day 1, when the morning dose will be given at the study site clinic. Subjects will be required to keep a pill diary that will be provided to them.

Also known as: INCB024360, IDO inhibitor

Epacadostat and pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 tyrosine kinase inhibitor (TKI).
• 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.
• Absolute neutrophil count ≥ 1.5 x 109/L.
• Platelets ≥ 100 x 109/L.
• Hemoglobin ≥ 9 g/dL (transfusion is acceptable to meet this criteria)
• Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN) OR calculated creatinine clearance ≥ 50 mL/min for subjects with creatinine levels \> 1.5 x institutional ULN.
• Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase ≤ 2.5 x ULN, or ≤ 5 x ULN in subjects with liver metastases.

You may not qualify if:

• 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.
• A diagnosis of another active malignancy with the following exceptions: basal or squamous cell carcinoma of the skin, in-situ carcinoma of the cervix, isolated elevation of prostate-specific antigen, indolent secondary malignancies not requiring active therapy, or with the approval of the principal investigator. Subjects with a completely treated prior malignancy and no evidence of disease for ≥ 2 years are eligible.
• Subjects with known active hepatitis B (HBV) or hepatitis C (HCV) infection as defined by the following (Hepatitis screening studies are required:
• Positive test for hepatitis B surface antigen
• Positive test for hepatitis C antibody and/ or hepatitis C quantitative viral load (Note: Subjects with a positive hepatitis C antibody and negative quantitative hepatitis C polymerase chain reaction (PCR) viral load are eligible)
• Subjects with a known history of HIV, including patients with controlled disease on antiretroviral therapy. HIV testing is not required as part of screening for this study.

Sponsors & Collaborators

• Columbia University: lead

Study Sites (2)

U-M Comprehensive Cancer Center

Ann Arbor, Michigan, 48109-0944, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

pembrolizumab; spartalizumab; epacadostat

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Results Point of Contact

• Title: Richard Carvajal, MD
• Organization: Northwell

rcarvajal2@northwell.edu

516-734-8900

Study Officials

• Richard D Carvajal, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2017
• First Posted: September 25, 2017
• Study Start: February 28, 2018
• Primary Completion: August 19, 2020
• Study Completion: August 19, 2020
• Last Updated: June 11, 2024
• Results First Posted: June 11, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)