ALCMI-005: Pembrolizumab and Epacadostat in Treating Patients With Extensive Stage Small Cell Lung Cancer

PRIMARY OBJECTIVES:

I. To assess the objective response rate (ORR) as measured by a modified Response Evaluation
Criteria in Solid Tumors (RECIST) version (v)1.1 in subjects with extensive stage small cell
lung cancer undergoing treatment with combination pembrolizumab and epacadostat.

SECONDARY OBJECTIVES:

I. To assess the progression free survival (PFS) as measured by a modified RECIST v1.1 in
subjects with extensive stage small cell lung cancer undergoing treatment with combination
pembrolizumab and epacadostat.

II. To assess the overall survival in subjects with extensive stage small cell lung cancer
undergoing treatment with combination pembrolizumab and epacadostat.

III. To assess the >= grade 3 drug related adverse event profile of combination pembrolizumab
and epacadostat in subjects with extensive stage small cell lung cancer.

TERTIARY OBJECTIVES:

I. To assess tumor genomics, T-cell, myeloid-derived suppressor cells, and receptors
(including PD-L1, IDO1, etc) in relation to response rates.

II. To assess cell free deoxyribonucleic acid (DNA) (cfDNA), cell free ribonucleic acid (RNA)
(cfRNA), micro RNA (miRNA), and exosomes as predictors for outcomes to treatment with
pembrolizumab and epacadostat in subjects with extensive stage small cell lung cancer and to
evaluate plasma for predictive markers for outcomes to therapy.

III. Blood samples will be also be stored for future evaluation.

OUTLINE:

Patients receive pembrolizumab intravenously (IV) on day 1 and epacadostat orally (PO) twice
daily (BID) on days 1-21. Treatment repeats every 21 days for up to 35 courses in the absence
of disease progression or unacceptable toxicity. Patients benefiting from treatment may
continue for an additional 17 courses.

After completion of study treatment, patients are followed up at 30 days, then every 12 weeks
thereafter.

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