Pembrolizumab and Epacadostat in Treating Participants with Advanced Thymic Cancer

Status: Active

Description

This phase II trial studies how well pembrolizumab and epacadostat works in treating participants with thymic cancer that has spread to other places in the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Epacadostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and epacadostat may work better in treating participants with advanced thymic cancer.

Eligibility Criteria

Inclusion Criteria

  • Histologic confirmation of thymic carcinoma (World Health Organization [WHO] classification)
  • Advanced disease (Masaoka staging) not amenable to curative treatment
  • At least 1 prior line of chemotherapy
  • Progression of disease must be documented prior to study entry
  • Absence of any autoimmune syndrome typically associated with thymomas but not thymic carcinomas (myasthenia gravis, pure red cell aplasia, etc.)
  • Be willing and able to provide written informed consent/assent for the trial
  • Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
  • Performed within 10 days of treatment initiation; absolute neutrophil count (ANC) ≥ 1,500 /mcL
  • Performed within 10 days of treatment initiation; platelets ≥ 100,000 / mcL
  • Performed within 10 days of treatment initiation; hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L
  • Performed within 10 days of treatment initiation; serum creatinine ≤ 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (CrCl) (glomerular filtration rate [GFR] can also be used in place of creatinine or CrCl) ≥ 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN * Creatinine clearance should be calculated per institutional standard
  • Performed within 10 days of treatment initiation; serum total bilirubin ≤ 1.5 X ULN or direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN
  • Performed within 10 days of treatment initiation; aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
  • Performed within 10 days of treatment initiation; international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (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
  • Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
  • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy

Exclusion Criteria

  • Has disease which is amenable to radical treatment with surgery or radiation or a combination of treatments
  • Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
  • Has had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not recovered (i.e., ≤ grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., ≤ grade 1 or at baseline) from adverse events due to a previously administered agent * Note: Subjects with ≤ grade 2 neuropathy 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
  • Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
  • 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
  • Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule; subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study; subjects with hypothyroidism stable on hormone replacement or Sjogren’s syndrome will not be excluded from the study
  • Has evidence of interstitial lung disease
  • Has a history of non-infectious pneumonitis that required steroids, or has a history of active pneumonitis
  • Has an active infection requiring systemic therapy
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Has known hypersensitivity to pembrolizumab (MK-3475) or its formulation
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Is pregnant or breastfeeding, or 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 trial treatment
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
  • Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
  • Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
  • Has received a live vaccine within 30 days prior to the first dose of trial treatment
  • Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications
  • Screening electrocardiography (ECG) with corrected QT (QTc) interval > 480 milliseconds (corrected by Fridericia); in the event that a single QTc is > 480 msec, the subject may enroll if the average QTc for 3 ECGs is < 480 msec
  • Prior receipt of an indoleamine 2,3-dioxygenase (IDO) inhibitor
  • Receipt of monoamine oxidase inhibitors (MAOIs) within 21 days before first dose of study treatment
  • History of serotonergic syndrome

Locations & Contacts

District of Columbia

Washington
MedStar Georgetown University Hospital
Status: Active
Contact: Giuseppe Giaccone
Phone: 202-687-7072

New Jersey

Hackensack
Hackensack University Medical Center
Status: In review
Contact: Martin E. Gutierrez
Phone: 551-996-5900

New York

New York
Memorial Sloan Kettering Cancer Center
Status: In review
Contact: Gregory J. Riely
Phone: 646-888-4199

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. Response rate.

SECONDARY OBJECTIVES:

I. Progression-free survival, overall survival, tolerability.

EXPLORATORY OBJECTIVES:

I. Correlate PDL-1 expression in tumor samples and outcome to treatment.

II. Develop conditionally reprogrammed cell from tumors whenever possible, in order to genetically characterize the tumor of origin.

III. Perform next-generation sequencing on tumors and correlate the molecular profile with treatment outcome.

IV. Assess IDO1 expression in tumor samples and correlate it to treatment outcome.

V. Explore kynurenin/tryptophan blood levels before and during treatment.

OUTLINE:

Participants receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and epacadostat orally (PO) every 12 hours (twice a day [BID]) every 3 weeks. Courses repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up at 30 days and then every 12 weeks for up to a year.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
MedStar Georgetown University Hospital

Principal Investigator
Giuseppe Giaccone

Trial IDs

Primary ID 2014-1315
Secondary IDs NCI-2018-00288
Clinicaltrials.gov ID NCT02364076