Clinical trial NCT03402880 (phase 2, status: withdrawn)
Conditions: extensive stage small cell lung carcinoma
ICD codes: D02.20, D02.21, D02.22
Drugs: epacadostat
SMILES: NS(=O)(=O)NCCNC1=NON=C1\C(NC1=CC(Br)=C(F)C=C1)=N\O
Reason stopped: 
    no patients enrolled
  
Eligibility criteria:

        Inclusion Criteria:

          -  Be willing and able to provide written informed consent/assent for the trial

          -  Subjects with histologically or cytologically confirmed small cell lung cancer and
             radiographic evidence of extensive stage disease

          -  Previous treatment with platinum based therapy for small cell lung cancer (eligibility
             not dependent on stage at time of platinum based therapy)

          -  Have measurable disease based on RECIST v1.1

          -  Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             performance scale

          -  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 without transfusion or erythropoietin (EPO)
             dependency (within 7 days of assessment) (performed within 10 days of treatment
             initiation)

          -  Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated
             creatinine clearance >= 60 mL/min for subject with creatinine levels > 1.5 X
             institutional ULN (glomerular filtration rate [GFR] can also be used in place of
             creatinine or creatinine clearance [CrCl]) (performed within 10 days of treatment
             initiation)

          -  Serum total bilirubin =< 1.2 X ULN OR conjugated bilirubin =< 1.2 x ULN; if an
             institutional ULN for conjugated bilirubin is not available, then conjugated bilirubin
             should be < 40% of total bilirubin to be considered eligible (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)

          -  Albumin >= 2.5 mg/dL (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 (performed
             within 10 days of treatment initiation)

          -  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 (performed within 10 days of treatment initiation)

          -  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 must be willing to use an adequate method of
             contraception 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

          -  Male subjects of childbearing potential must 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

               -  Note: abstinence is acceptable if this is the usual lifestyle and preferred
                  contraception for the subject

        Exclusion Criteria:

          -  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 4 weeks of the first dose of treatment

          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy > 10
             mg/day prednisone equivalents or any other form of immunosuppressive therapy within 7
             days prior to the first dose of trial treatment

          -  Has a known history of active TB (Bacillus tuberculosis); recommend documentation of
             inadequate treatment of latent or active TB

          -  Hypersensitivity to pembrolizumab, epacadostat or any of its excipients

          -  Corrected QT (QTc) > 480 ms: history or presence of an abnormal electrocardiogram
             (ECG) that, in the investigators 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 corrected JT (JTc) interval may be used in place of the QTc
             with sponsor approval; the JTc must be < 340 milliseconds if JTc is used in place of
             the QTc; subjects with left bundle branch block are excluded; QTc prolongation due to
             pacemaker may enroll if the JTc is normal

          -  Has had a prior anti-cancer monoclonal antibody (mAb) 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 or squamous cell carcinoma of the
             skin that has undergone potentially curative therapy or in situ cervical cancer

          -  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

          -  Has active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs); exceptions include vitiligo, controlled asthma, type I diabetes, Graves'
             disease, Hashimoto's disease, or with medical monitor approval; replacement therapy
             (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for
             adrenal or pituitary insufficiency, etc.) is not considered a form of systemic
             treatment

          -  Subjects who have had prior radiotherapy within 2 weeks of therapy; subjects must have
             recovered from all radiation-related toxicities, not require corticosteroids, and not
             have had radiation pneumonitis; a 1-week wash out is permitted for palliative
             radiation to non-CNS disease with medical monitor approval

          -  Has known history of non-infectious pneumonitis that required steroids, evidence of
             interstitial lung disease or active, non-infectious pneumonitis

          -  Has an active infection requiring systemic therapy

          -  Presence of a gastrointestinal condition that may affect drug absorption

          -  Subjects receiving monoamine oxidase inhibitors (MAOIs) within the 21 days before
             screening

          -  Any history of serotonin syndrome after receiving 1 or more serotonergic drugs

          -  Has a history of other malignancy within 2 years of study entry, with the exception of
             cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer,
             prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other
             noninvasive or indolent malignancy, or cancers from which the subject has been
             disease-free for >= 1 year following treatment with curative intent

          -  Clinically significant cardiac disease, including unstable angina, acute myocardial
             infarction within 6 months from day 1 of study drug administration, New York Heart
             Association class III or IV congestive heart failure, and arrhythmia requiring 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 subjects
             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 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, or anti-IDO1
             agent

          -  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 B virus [HBV] DNA detected) or hepatitis C (e.g., hepatitis C virus [HCV]
             RNA [qualitative] is detected)

          -  Has received a live vaccine within 30 days of planned start of study therapy

               -  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