A Study of Epacadostat, an IDO1 Inhibitor, in Combination With Pembrolizumab in Patients With Metastatic and/or Locally Advanced Sarcoma

NCT03414229 | Active Not Recruiting Phase 2 Results FDA Drug

• 1 other identifier: 17-508
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test any good and bad effects of the combination therapy of epacadostat and pembrolizumab and to determine how well the combination therapy works in the treatment of patients with sarcoma.

Conditions

Sarcoma

Keywords

Epacadostat; Pembrolizumab; 17-508

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Best Objective Response Rate

  by RECIST 1.1.

  by 24 weeks

Study Arms (4)

UPS, Liposarcoma or pleomorphic liposarcoma

EXPERIMENTAL

Undifferentiated Pleomorphic Sarcoma (UPS) or Liposarcoma (dedifferentiated or pleomorphic liposarcoma) Epacadostat 100mg Twice daily Continuously days 1-21 of each 3 week cycle Oral Pembrolizumab 200mg Every 3 weeks Day 1 of each 3 week cycle IV infusion

Drug: Epacadostat; Drug: Pembrolizumab

Leiomyosarcoma

EXPERIMENTAL

Epacadostat 100mg Twice daily Continuously days 1-21 of each 3 week cycle Oral Pembrolizumab 200mg Every 3 weeks Day 1 of each 3 week cycle IV infusion

Drug: Epacadostat; Drug: Pembrolizumab

Vascular Sarcoma Subtypes

EXPERIMENTAL

Including angiosarcoma and Epithelioid Hemangioendothelioma (EHE). Epacadostat 100mg Twice daily Continuously days 1-21 of each 3 week cycle Oral Pembrolizumab 200mg Every 3 weeks Day 1 of each 3 week cycle IV infusion

Drug: Epacadostat; Drug: Pembrolizumab

Other

EXPERIMENTAL

Epacadostat 100mg Twice daily Continuously days 1-21 of each 3 week cycle Oral Pembrolizumab 200mg Every 3 weeks Day 1 of each 3 week cycle IV infusion

Drug: Epacadostat; Drug: Pembrolizumab

Interventions

Epacadostat DRUG

100mg bid days 1-21

Leiomyosarcoma; Other; UPS, Liposarcoma or pleomorphic liposarcoma; Vascular Sarcoma Subtypes

Pembrolizumab DRUG

200mg/dose Day 1, Q 3 weeks

Leiomyosarcoma; Other; UPS, Liposarcoma or pleomorphic liposarcoma; Vascular Sarcoma Subtypes

Eligibility Criteria

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

You may qualify if:

• Male or female age ≥ 18 years at the time of informed consent
• Be willing and able to provide written informed consent/assent for the trial
• Be willing to comply with treatment protocol
• Subjects must have a histologically confirmed metastatic and/or locally advanced sarcoma
• Adequate performance status: ECOG 0 or 1/KPS 100-70%
• Subjects must have at least one prior line of systemic therapy (e.g. chemotherapy, immunotherapy, targeted or biological therapy) for their sarcoma. An exception to this criterion will be made for patients with sarcoma histological subtypes for which there is no known standard systemic therapy (e.g., chondrosarcoma). Any patient that refuses standard chemotherapy for the treatment of their disease is also considered eligible. Prior adjuvant therapy will not count provided it was completed more than 6 months previously.
• Presence of measureable disease per RECIST v1.1.Target lesions must not be chosen from a previously irradiated field unless there has been radiographically and/or pathologically documented tumor progression in that lesion prior to enrollment.
• All subjects must agree to pre-treatment tumor biopsy. Subjects in whom biopsy is technically not feasible or in whom would result in unacceptable risk, in the opinion of the investigator, may be exempted from the biopsy requirement with discussion with the principal investigator.
• Adequate organ function determined within 21 days of treatment initiation
• Hematological
• Absolute neutrophil count (ANC) ≥1,000 /mcL
• Platelets ≥75,000 / mcL
• Hemoglobin ≥8 g/dL or ≥5.0 mmol/L
• Renal
• °Serum creatinine OR Measured or calculateda creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR

You may not qualify if:

• Uncontrolled intercurrent illness including current active infection requiring systemic therapy or symptomatic congestive heart failure within 6 months
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• Evidence of clinically significant immunosuppression such as the following:
• Primary immunodeficiency state such as Severe Combined Immunodeficiency Disease
• Concurrent opportunistic infection
• Receiving systemic immunosuppressive therapy (\> 2 weeks) including oral steroid doses \> 10 mg/day of prednisone or equivalent within 7 days prior to enrollment. However, in the setting of non-immune mediated indications for steroid use, chronic/active low dose steroid use may be permitted at the discretion of the principal investigator. The dose of steroid allowed in this setting is also at the discretion of the principal investigator. (Use of inhaled or topical steroids is permitted.)
• History or evidence of symptomatic autoimmune disease (e.g., pneumonitis, glomerulonephritis, vasculitis, or other), or history of active autoimmune disease that has required systemic treatment (i.e., use of corticosteroids, immunosuppressive drugs or biological agents used for treatment of autoimmune diseases) in past 2 years prior to enrollment. Replacement therapy (e.g., thyroxine for hypothyroidism, insulin for diabetes or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment for autoimmune disease.
• Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies) disease
• Has known active Hepatitis B (e.g., Hepatitis B Virus PCR is detected) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
• Patients who have received a live vaccine within 30 days of the start date of the planned study therapy. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
• Has a known history of active TB (Bacillus Tuberculosis)
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 2 weeks of the first dose of treatment.
• Has had a prior chemotherapy, immunotherapy, biological therapy, targeted small molecule therapy, or radiation therapy within 3 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to previously administered agent.
• Note: Subjects with ≤ Grade 2 neuropathy, alopecia or hypothyroidism are an exception to this criterion and may qualify for the study.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy events due to a previously administered agent.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Incyte Corporation: collaborator
• Merck Sharp & Dohme LLC: collaborator
• M.D. Anderson Cancer Center: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Sarcoma

Interventions

epacadostat; pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Results Point of Contact

• Title: Dr. Sanda D'Angelo, MD
• Organization: Memorial Sloan Kettering Cancer Center

dangelos@mskcc.org

646-888-4159

Study Officials

• Sandra D'Angelo, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single-center, phase II study to evaluate the efficacy of the IDO1 inhibitor, epacadostat, given in combination with the anti-PD1 monoclonal antibody, pembrolizumab, for patients with metastatic and/or locally advanced grade sarcomas.

Study Record Dates

• First Submitted: January 23, 2018
• First Posted: January 29, 2018
• Study Start: January 23, 2018
• Primary Completion: September 9, 2024
• Study Completion (Estimated): January 1, 2027
• Last Updated: April 23, 2026
• Results First Posted: May 2, 2025

Record last verified: 2026-04

Locations

US (1)