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

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ClinicalTrials.gov Identifier: NCT03414229
Recruitment Status : Recruiting
First Posted : January 29, 2018
Last Update Posted : September 16, 2019
Sponsor:
Collaborators:
Incyte Corporation
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

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.

Condition or disease Intervention/treatment Phase
Sarcoma Drug: Epacadostat Drug: Pembrolizumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Epacadostat (INCB024360) in Combination With Pembrolizumab in Patients With Locally Advanced/Metastatic Sarcoma
Actual Study Start Date : January 23, 2018
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : January 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: UPS, Liposarcoma or pleomorphic liposarcoma
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
100mg bid days 1-21

Drug: Pembrolizumab
200mg/dose Day 1, Q 3 weeks

Experimental: Leiomyosarcoma
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
100mg bid days 1-21

Drug: Pembrolizumab
200mg/dose Day 1, Q 3 weeks

Experimental: Vascular Sarcoma Subtypes
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
100mg bid days 1-21

Drug: Pembrolizumab
200mg/dose Day 1, Q 3 weeks

Experimental: Other
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
100mg bid days 1-21

Drug: Pembrolizumab
200mg/dose Day 1, Q 3 weeks




Primary Outcome Measures :
  1. number of patients with best objective response rate [ Time Frame: by 24 weeks ]
    by RECIST 1.1.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

    ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN aCreatinine clearance should be calculated per institutional standard.

  • Hepatic

    • Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN
    • AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
    • Albumin ≥ 2.5 mg/dL
  • Coagulation

    • International Normalized Ratio 52 or Prothrombin Time ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
    • Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Women of childbearing potential must have a negative serum pregnancy test at screening and ≤ 72 hours prior to day 1 of study treatment.
  • Male and female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in Section 11.7, for the course of the study through 120 days after the last dose of study medication.

Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

Exclusion Criteria:

  • 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.
  • Presence of a gastrointestinal condition that may affect drug absorption
  • Known allergy or reaction to any component of either study drug formulation
  • Women who are pregnant or breast feeding
  • Subjects expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of study treatment(s).
  • Inability to comply with protocol required procedures
  • Subjects receiving Monoamine Oxidase Inhibitors (MAOIs) or drug which has significant MAOI activity (meperidine, linezolid, methylene blue) within the 21 days before screening.
  • Any history of Serotonin Syndrome (SS) after receiving serotonergic drugs.
  • History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful. Screening QTc interval 480 milliseconds is excluded. In the event that a single QTc is ≥ 480 milliseconds, the subject may enroll if the average QTc for the 3 ECGs is < 480 milliseconds. For subjects with an intraventricular conduction delay (QRS interval > 120 milliseconds), the JTc interval may be used in place of the QTc with the approval of the principal investigator. The JTc must be < 340 milliseconds if JTc is used in place of the QTc. Subjects with left bundle branch block are excluded.

Note: QTc prolongation due to pacemaker may enroll if the JTc is normal.

  • Use of any UGT1A9 inhibitor from screening through follow-up period, including the following: diclofenac, imipramine, ketoconazole, mefenamic acid, and probenecid.
  • History of prior therapy with an IDO1 inhibitor in combination with an anti-PD-1/anti-PD-L1 agent/any other drug specifically targeting checkpoint pathways. Patients who have received prior therapy with single agent anti-PD-1/anti-PD-L1 therapy or single agent IDO1 inhibitor will be eligible for this study.
  • Presence of any other concurrent active malignancy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03414229


Contacts
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Contact: Sandra D' Angelo, MD 646-888-4159 dangelos@mskcc.org
Contact: William Tap, MD 646-888-4163

Locations
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United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Sandra D' Angelo, MD    646-888-4159      
Contact: William Tap, MD         
Principal Investigator: Sandra D' Angelo, MD         
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Incyte Corporation
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: Sandra D'Angelo, MD Memorial Sloan Kettering Cancer Center

Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT03414229     History of Changes
Other Study ID Numbers: 17-508
First Posted: January 29, 2018    Key Record Dates
Last Update Posted: September 16, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Memorial Sloan Kettering Cancer Center:
Epacadostat
Pembrolizumab
17-508
Additional relevant MeSH terms:
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Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents