A Randomized, Double-Blind Phase 2 Study of Ruxolitinib or Placebo in Combination With Pemetrexed/Cisplatin and Pemetrexed Maintenance for Initial Treatment of Subjects With Nonsquamous Non-Small Cell Lung Cancer That Is Stage IIIB, Stage IV, or Recurrent

Overall, the safety profile of ruxolitinib in the PV population treated with
ruxolitinib is generally consistent with what was observed in the MF
population. Ruxolitinib was generally well tolerated in patients with PV and
only a small proportion of patients discontinued
ruxolitinib due to AEs (3.6%). Most of the AEs have been managed by dose
adjustments. Hematological toxicities were less frequent and less severe in
patients with PV as compared to those observed in patients with MF.
No new safety signals emerged from a study in pancreatic cancer in combination
with capecitabine.
The AE profile of the compound has been assessed in 198 healthy volunteers,
subjects with various degrees of renal (n=32) or hepatic (n=24) impairment, and
in patients with RA (n=59) receiving ruxolitinib: AEs were, in general, mild
and resolved without interventions.
A thorough QT study was conducted in 50 healthy subjects. There was no
indication of a QT/QTc prolonging effect of ruxolitinib in single doses up to a
supra-therapeutic dose of 200mg indicating that ruxolitinib has no effect on
cardiac repolarization.

Primary Objectives:
• Part 1: To evaluate the safety and tolerability of ruxolitinib in combination
with pemetrexed/cisplatin and select a dose for further evaluation
• Part 2: To evaluate and compare the overall survival of subjects with
nonsquamous non-small cell lung cancer (NSCLC) that is Stage IIIB, Stage IV, or
recurrent when treated with ruxolitinib or placebo in combination with
pemetrexed/cisplatin and subsequently pemetrexed maintenance
Secondary Objectives:
• To evaluate and compare the efficacy of the 2 treatment arms with respect to
progression-free survival (PFS)
• To evaluate and compare the efficacy of the 2 treatment arms with respect to
overall tumor response and duration of response
• To evaluate and compare the safety and tolerability of ruxolitinib in
combination with pemetrexed/cisplatin versus pemetrexed/cisplatin alone
Exploratory Objectives:
• To evaluate changes in pharmacodynamic (PD) and tumor markers
• To evaluate pharmacokinetics (PK) of ruxolitinib, cisplatin, and pemetrexed
alone or in combination
• To evaluate molecular signatures that may be associated with response or
resistance to treatment if sufficient numbers of biopsy samples are available
• To evaluate and compare the 2 treatment arms with respect to changes in
health-related quality of life (HR-QOL)
• To evaluate and compare the 2 treatment arms with respect to changes in body
weight relative to baseline.

This is a Phase 2 study in subjects with nonsquamous NSCLC that is Stage IIIB,
Stage IV, or recurrent. The study consists of 2 parts. Part 1 is an open
label safety run-in phase designed to assess the safety and tolerability of the
combination of ruxolitinib plus pemetrexed/cisplatin and to select an
appropriate dose of ruxolitinib in this patient population. Part 2 is planned
to be a randomized, double-blind Phase 2 study with 2 treatment arms:
ruxolitinib plus pemetrexed/cisplatin versus placebo plus
pemetrexed/cisplatin. Maintenance therapy with ruxolitinib or placebo in
combination with pemetrexed, based on the original treatment assignment, will
be allowed for subjects eligible for maintenance therapy. In Part 1, if a dose
of ruxolitinib with concomitant granulocyte colony-stimulating factor (GCSF) is
selected for Part 2, then Part 2 will be conducted as a randomized, unblinded,
open-label study.
Part 1: Safety Run-in Phase. The safety run-in portion will test up to 2 doses
of ruxolitinib (15 mg twice daily (BID) and 10 mg BID) in combination with a
single standard dose on Day 1 of pemetrexed/cisplatin (500 mg/m2 pemetrexed
administered as an intravenous infusion over 10 minutes/75 mg/m2 cisplatin
infused over 2 hours beginning 30 ± 5 minutes after the end of the pemetrexed
infusion) for a 21-day assessment period (1 cycle designated Treatment Cycle 1
or TCycle 1). Initially, 9 subjects will be enrolled in Cohort 1 and will
receive 15 mg ruxolitinib BID. At the end of 21 days, subjects who took at
least 34 doses of ruxolitinib during the 21-day cycle (ie, took BID doses for
17 of the 21 days) OR experienced a dose-limiting toxicity (DLT) will be
included in the evaluation cohort. Additional subjects will be enrolled to
achieve a minimum of 9 subjects in the evaluation cohort if there are
discontinuations or dose interruptions that result in a subject being
nonevaluable.

After evaluation, the following actions will occur, involving up to 4
successive cohorts:
Cohort 1 (9 Subjects) : 15 mg ruxolitinib BID plus pemetrexed/cisplatin (single
intravenous infusion doses on Day 1).
- DLTs observed : < 3 Action taken : Begin randomized portion of study using 15
mg ruxolitinib BID.
- DLTs observed : >= 3 Action taken : Enroll Cohort 2.

Cohort 2 (9 Subjects) :10 mg BID ruxolitinib plus pemetrexed/cisplatin (single
intravenous infusion doses on Day 1).
- DLTs observed : < 3 Action taken : Begin randomized portion of study using 10
mg ruxolitinib BID.
- DLTs observed : >= 3 Action taken : If at least 1 DLT was based on
neutropenia, enroll Cohort 3. If DLTs are not neutropenia-related, terminate
study.

Cohort 3 (9 Subjects) :10 mg ruxolitinib BID plus pemetrexed/cisplatin (single
intravenous infusion doses on Day 1) plus GCSF.
- DLTs observed : < 3 Action taken : Enroll Cohort 4.
- DLTs observed : >= 3 Action taken : Terminate the study.

Cohort 4 (9 Subjects) : 15 mg BID ruxolitinib plus pemetrexed/cisplatin (single
intravenous infusion doses on Day 1) plus GCSF.
- DLTs observed : < 3 Action taken : Begin randomized portion of study using 15
mg ruxolitinib BID and prophylactic GCSF support.
- DLTs observed : >= 3 Action taken : Begin randomized portion of study using 10
mg ruxolitinib BID and prophylactic GCSF support.
The maximum tolerated dose (MTD) is the highest dose level tested that is
considered tolerated on the basis of fewer than 3 DLTs in a cohort of 9
subjects.

If the MTD is exceeded in Cohort 1 or 2 and >= 1 DLT was neutropenia (see
hematologic DLTs below), a third cohort using 10 mg ruxolitinib BID and
pemetrexed/cisplatin with prophylactic GCSF will be enrolled. In this case,
GCSF will be given as pegfilgrastim or as filgrastim, if the investigative site
uses the latter as their standard for GCSF. Evaluation of the 10 mg
ruxolitinib BID combination with pemetrexed/cisplatin and prophylactic GCSF
support will follow the same decision scheme; the study will be terminated if
10 mg ruxolitinib BID cannot be tolerated in combination with
pemetrexed/cisplatin and GCSF prophylactic support as evidenced by an incidence
rate of >= 33% DLTs in the 21-day evaluation period. If 10 mg ruxolitinib BID
with GCSF prophylactic support is adequately tolerated, a fourth cohort to
explore the safety and tolerability of 15 mg ruxolitinib BID with GCSF
prophylactic support will be enrolled. Part 2 of the study will proceed with
either 15 mg or 10 mg ruxolitinib BID, with prophylactic GCSF support, based on
Part 1 of the study.
After the 21-day safety evaluation period, safety run-in subjects may receive 3
additional cycles of pemetrexed/cisplatin (Treatment Cycles or TCycles 2, 3,
and 4) in combination with ruxolitinib, and subjects with an objective response
or stable disease (SD) may receive up to 2 additional cycles (TCycles 5 and 6),
as long as adequately tolerated and disease progression has not occurred,
followed by maintenance pemetrexed (Maintenance Cycles or MCycles) in
combination with ruxolitinib, with study visits each 21 day cycle.
Measurements and procedures will follow those described in Section 4.1.3.2 for
the randomized, double-blind phase. Ruxolitinib doses will be determined by
the degree of thrombocytopenia and neutropenia observed in the safety run-in
cohort and will follow the dose adjustment rules described in the body of the
Protocol.
Adverse events (AEs) occurring during the safety run-in portion of the study
will be considered to be DLTs if they are not clearly related to the underlying
disease, its progression, a comorbidity, or concomitant medication (excluding
pemetrexed or cisplatin), or if they are transient (<= 72 hours) abnormal
laboratory values without associated clinically significant signs or symptoms
based on investigator determination. A DLT will be defined as an AE that is
new in onset and meets any of the following criteria, using the CTCAE v4.03
toxicity grading scale:
Hematologic toxicities:
• Grade 3 thrombocytopenia with bleeding requiring transfusion of red blood
cells
• Grade 4 thrombocytopenia
• Febrile neutropenia (absolute neutrophil count [ANC] < 1.0 × 109/L and fever
> 101°F/38.3°C)
• Grade 4 neutropenia that does not recover to <= Grade 2 within 3 days after
holding the ruxolitinib dose or requiring myeloid growth factors
NOTE: Ruxolitinib is suspected to cause transient decreases in white blood
cells (WBCs) due to margination; therefore, DLT rules require neutropenia to
persist after holding ruxolitinib for 3 days. Where the clinical status of the
subject allows, investigators are encouraged to wait 24 hours before starting
myeloid growth factors to determine if WBC margination is contributing to the
degree of neutropenia.
Nonhematologic toxicity:
• Any >= Grade 3 nonhematologic toxicity EXCEPT:
* Nausea, vomiting, and diarrhea adequately controlled with medical therapy
within 48 hours
* Changes in cholesterol levels
Grade 3 or 4 laboratory abnormalities should be confirmed within 72 hours.
Part 1 will be conducted at selected clinical study sites (in United States
only). Enrollment will be controlled by distribution of enrollment slots to
the clinical sites by the sponsor or its designee. The sponsor will conduct
approximately weekly safety teleconferences with the investigators
participating in Part 1 to review subject status and safety findings to ensure
safe, appropriate dosing.
Part 2: Randomized, Double-Blind Phase. Part 2 will be enrolled and conducted
provided an MTD can be established for ruxolitinib in combination with
cisplatin/pemetrexed in Part 1 of the study. The randomized, double-blind
phase of the study will enroll approximately 120 subjects, randomized 1:1 and
stratified for a modified Glasgow prognostic score (mGPS) of 1 or 2 into 2
treatment arms:
• Arm 1: Ruxolitinib (at dose selected from safety run-in phase) plus
pemetrexed 500 mg/m2 administered as an intravenous infusion over 10 minutes
and cisplatin 75 mg/m2 infused over 2 hours beginning 30 ± 5 minutes after the
end of the pemetrexed infusion on Day 1 of each 21 day cycle for up to 4 cycles
(Treatment Cycles or TCycles 1, 2, 3, and 4), as long as adequately tolerated
and disease progression has not occurred. Two additional cycles (TCycles 5 and
6) may be administered in subjects with an objective response or SD, as long as
adequately tolerated and disease progression has not occurred. Subjects will
then receive maintenance pemetrexed (Maintenance Cycles or MCycles) (if
adequately tolerated) with ruxolitinib.
• Arm 2: Matching placebo plus pemetrexed 500 mg/m2 administered as an
intravenous infusion over 10 minutes and cisplatin 75 mg/m2 infused over 2
hours beginning 30 ± 5 minutes after the end of the pemetrexed infusion on Day
1 of each 21 day cycle for up to 4 cycles (TCycles 1, 2, 3, and 4), as long as
adequately tolerated and disease progression has not occurred. Two additional
cycles (MCycles 5 and 6) may be administered in subjects with an objective
response or SD, as long as adequately tolerated and disease progression has not
occurred. Subjects will then receive maintenance pemetrexed (MCycles) (if
adequately tolerated) with matching placebo.
In Part 1, if a dose of ruxolitinib with concomitant GCSF is selected for Part
2, then Part 2 will be conducted as a randomized, unblinded, open label study.
In this case, the control group will utilize cisplatin/pemetrexed with no
placebo. Maintenance therapy with pemetrexed and study drug will not include
prophylactic GCSF if the induction therapy with pemetrexed/cisplatin requires
primary or secondary GCSF prophylaxis.

Study Schedule/Procedures:
Safety Run-in Phase: Subjects will have regularly scheduled study visits at
screening and baseline (Day 1). Blood samples will be drawn at each visit to
monitor hematologic and serum chemistry parameters. Subjects will also have
brief study visits at Day 8 and Day 15, primarily for hematology assessments.
The prestudy radiographic measurement for tumor size will be performed at the
screening visit. After 21 days, safety run-in subjects may receive up to 3
additional cycles of pemetrexed/cisplatin (TCycles 2, 3, and 4) in combination
with ruxolitinib, and subjects with an objective response or SD may receive up
to 2 additional cycles (TCycles 5 and 6), as long as adequately tolerated and
disease progression has not occurred, followed by maintenance pemetrexed
(MCycles) in combination with ruxolitinib at the same cohort-specific dose or
as adjusted based on the dose reduction rules described in the body of the
Protocol. Subjects will have a regularly scheduled study visit at the clinical
site on Day 1 (± 3 days) of each cycle and a brief study visit, primarily to
perform hematology assessment, on Day 10 (± 4 days) of each cycle.
Randomized, Double-Blind Phase: Subjects will have a regularly scheduled study
visit at the clinical site at screening, baseline (Day 1), and every 3 weeks (±
3 days) where blood samples will be collected and assessments conducted. All
laboratory assessments will be performed using a central laboratory except for
hematology.
Subjects will also have brief study visits at the study clinic laboratory (or
as described in the Laboratory Manual) on Day 10 of each cycle (± 4 days),
primarily to provide blood samples for hematology. Additional monitoring of
hematology or serum chemistry parameters may be performed at the investigator's
discretion.
Radiographic tumor assessments (typically computed tomography scan) will be
conducted every 6 weeks until disease progression. The prestudy radiographic
measurement for tumor size will be conducted during the 28 day screening
period. Subjects discontinued from study treatment who have not progressed
will still be assessed every 6 weeks until disease progression, beginning new
anticancer therapy, or death.
After discontinuation of study treatment for disease progression, laboratory
and nonradiographic assessments will cease and follow-up will occur every 6
weeks for subsequent anticancer therapies and survival. After the final
primary analysis is performed, follow-up for anticancer treatments and survival
will be reduced to every 12 weeks.
Premedication/Concomitant Medication Treatments: All subjects will be
instructed to take a low dose folic acid preparation or multivitamin with folic
acid on a daily basis. At least 5 daily doses of folic acid must be taken
during the 7 day period preceding the first dose of pemetrexed/cisplatin, and
dosing will continue during the full course of pemetrexed-containing therapy
and for 4 weeks after the last dose of pemetrexed. Subjects must also receive
1 intramuscular injection of vitamin B12 during the week preceding the first
dose of pemetrexed/cisplatin and every 3 cycles during pemetrexed-containing
therapy. Subjects will be instructed to take antiemetic medications during
cycles where pemetrexed/cisplatin or pemetrexed are used. Subjects must be
pretreated with 4 mg dexamethasone BID (or equivalent) the day before, the day
of, and the day after each infusion with pemetrexed/cisplatin or pemetrexed.
Note that alternatives to BID dexamethasone are described in the body of the
Protocol. If required based on the results from the safety run-in phase, GCSF
will be administered as a single subcutaneous injection of 6 mg pegfilgrastim
(Neulasta® or its equivalent) on Day 2 of each 21-day cycle, or as filgrastim
(Neupogen® or its equivalent) if the investigative site uses the latter as
their standard for GCSF.

Side Effects from Ruxolitinib
The risks of ruxolitinib may not be fully known, and may vary depending upon
the disease you are being treated for. Therefore, you will be informed of the
important symptoms or medical events (called *adverse events*) that have
occurred frequently in patients who had serious blood conditions called
myelofibrosis (MF) and polycythemia vera (PV). You will also be informed of
any adverse events that were rare but serious and might have been related to
the study drug. During your participation, you will be given any new
information that may affect your willingness to start or continue in the study
You should discuss the risks listed here with your Study Doctor. Many side
effects go away shortly after the study drug is stopped, but in rare cases they
may be serious, long lasting, and/or permanent, and may even cause death. If
you experience any of the described symptoms or have any other problems, you
must immediately tell the appropriate study staff member or the Study Doctor.
If you feel that these symptoms or side effects are life threatening seek
medical assistance immediately.
The following adverse events were reported as common side effects (occurring in
at least 1%) or very common (occurring in at least 10%) of patients who were
treated with ruxolitinib for MF or for PV.
Very Common (at least 10%)
• Anemia (low red blood cells)
• Thrombocytopenia (low platelets)
• Bruising
• Neutropenia (low white blood cells)
• Raised ALT and AST (blood proteins that may indicate mild liver damage)
• Hypercholesterolemia (increase in cholesterol)
• Hypertriglyceridemia (increase in triglycerides)
• Dizziness
• Headache
• Urinary tract infections
• Weight gain
Common (more than 1% but less than 10%)
• Flatulence (gas)
• Constipation
• Herpes zoster (shingles)
• Hypertension (high blood pressure)
Ruxolitinib may cause low blood cell counts (white blood cells, red blood cells
and platelets). If your white blood cell count becomes low while you take the
drug, this means you may have an increased chance of getting an infection,
including urinary tract infections and viral infections. You will be checked
for any signs of infection before starting ruxolitinib and any serious
infections should be treated before you start ruxolitinib; your physician will
check you carefully for signs of infection while you are being treated. You
also may become anemic (low red blood cell count) while you take the study
drug, and that may cause you to feel fatigued or short of breath. If your
platelet count becomes low while you take the study drug, it may lead to
bleeding and/or bruising. In some people taking ruxolitinib, the decreases in
blood cell counts have been severe. In most cases, low blood cell counts can
be reversed by stopping the study drug temporarily or reducing the dose; you
will be checked often for this side effect while on study. If your blood cell
counts do not recover quickly, the study drug may be stopped for a longer
duration to allow the blood cell counts to recover.
Uncommon (occurring in fewer than 1% of patients)
These events are events that were uncommon, but occurred ruxolitinib treatment
and are potentially serious.
• Non-melanoma skin cancers (NMSCs) are skin cancers such as basal cell cancer
or squamous cell cancer that usually develop on the sun-exposed areas of skin,
and commonly require surgery to remove. NMSCs have been reported in patients
with MF or PV who were treated with ruxolitinib. Most of these patients had
histories of extended treatment with medications known to increase the risk of
NMSC, and had NMSC or pre-cancerous skin lesions before being treated with
ruxolitinib. It is not known whether or not ruxolitinib contributed to these
cases of NMSC. Periodic skin examination is recommended for patients who are
at increased risk for skin cancer.
(The following conditions have occurred in patients with MF who were treated
with ruxolitinib)

• Tuberculosis (TB) has occurred in a small number of patients (less than 1%)
with MF who received ruxolitinib, but it is not known whether this was due to
MF, ruxolitinib, or other factors that are known to increase the risk of
tuberculosis (such as diabetes, bronchitis, asthma, smoking, emphysema, or
steroid use). Tell you study doctor if you have been treated for TB in the
past, or have ever had a positive skin test for TB.
• About one week following interruption or discontinuation of ruxolitinib, some
patients with MF experienced a return of symptoms (such as fatigue, bone pain,
fever, itching, night sweats, weight loss, or an enlarged spleen). There have
been cases of MF patients stopping ruxolitinib during another ongoing illness
who became more severely ill, but it was not clear whether stopping ruxolitinib
therapy contributed to the patients* conditions worsening.
• A rare disease called progressive multifocal leukoencephalopathy (PML) has
been reported during ruxolitinib treatment for MF. PML comes from a viral
infection that causes brain damage and can be fatal. It is unknown whether
this was due to ruxolitinib treatment since PML has occurred in patients with
blood cancers, including MF, who were not treated with ruxolitinib. Tell your
study doctor immediately if you have any of the following symptoms or if anyone
close to you notices that you have any of these symptoms: confusion or problems
thinking, loss of balance or problems walking, clumsiness, difficulty speaking,
decreased strength or weakness on one side of your body, blurred and/or loss of
vision.
Side Effects from Pemetrexed and Cisplatin When Given Together
The bullet points below provide the frequency and severity of adverse reactions
that have been reported in more than 5% of 839 people with NSCLC (165 people)
who were randomized to study and received pemetrexed plus cisplatin.
Reaction - Pemetrexed/Cisplatin (all grade toxicities - All adverse reactions =
90 %)
Laboratory:
• Hematologic
o Anemia - 33%
o Neutropenia - 29%
o Leukopenia - 18%
o Thrombocytopenia - 10%
• Renal
o Creatinine Elevation - 10%
Clinical:
• Constitutional Symptoms
o Fatigue - 43%
• Gastrointestinal
o Nausea - 56%
o Vomiting - 40%
o Anorexia - 27%
o Constipation - 21%
o Stomatitis/Pharyngitis - 14%
o Diarrhea - 12%
o Dyspepsia/heartburn - 5%
• Neurology
o Neuropathy - Sensory - 9%
o Taste disturbance - 8%
• Dermatology/Skin
o Alopecia - 12%
o Rash/Desquamation - 7%
Reaction - Pemetrexed/Cisplatin (grade 3 + 4 toxicities - All adverse reactions
= 37 %)
Laboratory:
• Hematologic
o Anemia - 6%
o Neutropenia - 15%
o Leukopenia - 5%
o Thrombocytopenia - 4%
• Renal
o Creatinine Elevation - 1%
Clinical:
• Constitutional Symptoms
o Fatigue - 7%
• Gastrointestinal
o Nausea - 7%
o Vomiting - 6%
o Anorexia - 2%
o Constipation - 1%
o Stomatitis/Pharyngitis - 1%
o Diarrhea - 1%
You should get medical help and call your study doctor or the study staff right
away if you experience any of the following:
• Fever of 38°C (100.4°F) for more than 1 hour
• Confusion or hallucinations (sensing things that aren*t real but made up by
the mind)
• Difficulty breathing
• A new rash
• Trouble swallowing, drooling or swelling of the face, neck or tongue
• Increased pain
• Headache
• Abdominal pain
• Constipation or uncontrollable diarrhea
• Uncontrolled nausea and or vomiting
• Bleeding
• Swelling in the arms or legs

Side Effects from Pemetrexed When Used for Maintenance Therapy
The bullet points below provide the frequency and severity of adverse reactions
reported in more than 5% of the 438 people with NSCLC who received ALIMTA®
(pemetrexed) maintenance and the 218 people with NSCLC who received placebo
following a platinum-based induction therapy. All people received study drug
immediately following 4 cycles of platinum-based treatment for locally advanced
or metastatic NSCLC. People in both study arms were fully supplemented with
folic acid and vitamin B12.
Reaction - Pemetrexed (all grade toxicities - All adverse reactions = 66 %)
Laboratory:
• Hematologic
o Anemia - 15%
o Neutropenia - 6%
o Leukopenia - 6%
• Hepatic
o Increased ALT - 10%
o Increased AST - 8%
Clinical:
• Constitutional Symptoms
o Fatigue - 25%
• Gastrointestinal
o Nausea - 19%
o Anorexia - 19%
o Vomiting - 9%
o Mucositis/stomatitis - 7%
o Diarrhea - 5%
• Infection - 5%
• Neurology
o Neuropathy - Sensory - 9%
• Dermatology/Skin
o Rash/Desquamation - 10%
Reaction - Pemetrexed (grade 3 - 4 toxicities - All adverse reactions = 16 %
Laboratory:
• Hematologic
o Anemia - 3%
o Neutropenia - 3%
o Leukopenia - 2%
Clinical:
• Constitutional Symptoms
o Fatigue - 5%
• Gastrointestinal
o Nausea - 1%
o Anorexia - 2%
o Mucositis/stomatitis - 1%
o Diarrhea - 1%
• Infection - 2%
• Neurology
o Neuropathy - Sensory - 1%

Reaction - Placebo (all grade toxicities - All adverse reactions = 37 %
Laboratory:
• Hematologic
o Anemia - 6%
o Leukopenia - 1%
• Hepatic
o Increased ALT - 4%
o Increased AST - 4%
Clinical:
• Constitutional Symptoms
o Fatigue - 11%
• Gastrointestinal
o Nausea - 6%
o Anorexia - 5%
o Vomiting - 1%
o Mucositis/stomatitis - 2%
o Diarrhea - 3%
• Infection - 2%
• Neurology
o Neuropathy - Sensory - 4%
• Dermatology/Skin
o Rash/Desquamation - 3%
Reaction - Placebo (grade 3 - 4 toxicities - All adverse reactions = 4 %
Laboratory:
• Hematologic
o Anemia - 1%
o Leukopenia - 1%
Clinical:
• Constitutional Symptoms
o Fatigue - 1%
• Gastrointestinal
o Nausea - 1%
Some people in the study will get placebo instead of ruxolitinib. Placebo is a
tablet that looks like ruxolitinib, but has no drug in it. If you take placebo
during the study, it is possible that your condition may get worse. Please ask
the study doctor or study staff if you have any questions about placebo.

Additional Common Side Effects When Ruxolitinib, Pemetrexed/Cisplatin are Used
Together
The side effects of using ruxolitinib/pemetrexed/cisplatin together are
unknown. Both ruxolitinib and pemetrexed/cisplatin can cause neutropenia (low
white blood cell count, white blood cells help you fight infections so you may
be more likely to develop an infection) and thrombocytopenia (low platelet
count). Platelets help your blood clot so a low platelet count may put you at
risk for bleeding. The study staff will watch your blood work for signs of
these two problems and may change the dose of your study drug if needed.
It is possible that taking ruxolitinib, pemetrexed, and cisplatin may change
how your regular medications, vaccines, or supplements work. It is very
important that you tell the study doctor about any medications, supplements, or
vaccines before you take them during the study.
Please tell the study doctor or study staff right away if you have any side
effects. Please tell them if you have any other problems with your health or
the way you feel during the study, whether or not you think these problems are
related to the study drug.
Some side effects are related to required medications and supplements to study
procedures or are risks of allergic reaction. For more information see Appendix
2.
Risks of Pregnancy or Fathering a Child
The risks to an unborn human fetus or a nursing child from ruxolitinib are not
known. Some drugs cause premature (early) birth or birth defects.
Pemetrexed/cisplatin may harm the fetus. Tell your study doctor if you are
pregnant, plan to become pregnant, or are breast-feeding. You should not become
pregnant or breast-feed while you are in this study. If you become pregnant
during this study, contact the study doctor or study staff.
Women who are pregnant or nursing a child may not participate in this study.
You must confirm that, to the best of your knowledge, you are not now pregnant,
and that you do not intend to become pregnant or you do not intend to father a
child during the study. If there is any possibility that you may become
pregnant or father a child during the study, the Study Doctor will discuss
appropriate birth control measures with you.
Female subjects who are able to have children must agree to take appropriate
precautions to avoid pregnancy (with at least 99% certainty) from screening
through the follow-up visit. Male subjects must agree to take appropriate
precautions to avoid fathering a child (with at least 99% certainty) from
screening through the follow-up visit.
If you are female and suspect that you have become pregnant during the study,
you must notify the Study Doctor immediately, and you have to stop study drug
dosing immediately. You will not be able to continue in the study if you become
pregnant. If you become pregnant, the study doctor will medically follow the
pregnancy until delivery to monitor you and your child's safety. The study
doctor will report the pregnancy and outcome to the Sponsor (Incyte
Corporation).
If you father a child during your participation in the study, you must notify
the Study Doctor immediately. If your partner becomes pregnant, your Study
Doctor will ask to medically follow the pregnancy until delivery in order to
monitor your partner*s and your child*s safety. The study doctor will report
the pregnancy to the Sponsor (Incyte Corporation). The Sponsor may request to
track your partner*s pregnancy.