A PHASE 1, OPEN-LABEL, DOSE ESCALATION STUDY OF PF-04518600 AS A SINGLE AGENT AND IN COMBINATION WITH PF-05082566 IN PATIENTS WITH SELECTED LOCALLY ADVANCED OR METASTATIC CANCERS

Immunotherapy offers the opportunity to not only stop tumor growth, but also
decrease the rate of tumor recurrence. By activating and expanding tumor
associated antigen T cells, it may be possible to enhance tumor immunity.
However, T cell activation is not mediated by antigen stimulation alone.
Instead, co stimulatory receptors are required. OX40 (CD134) and 4-1BB (CD137)
are co stimulatory receptors that act on antigen stimulated T cells but not
native T cells. OX40 plays a key role in T cell survival, proliferation, and
activation. Upon OX40 ligand (also known as OX40L, CD252 or TNFSF4 [tumor
necrosis factor (ligand) superfamily, member 4]) binding, OX40 signaling
upregulates anti apoptotic molecules including B cell lymphoma 2 (Bcl 2), Bcl
xL, and survivin, and increases interleukin 2 (IL 2), IL 4, IL 5, and
interferon gamma (IFN *) cytokine secretion. Similarly, activation of 4-1BB
signaling leads to an upregulation of pro-survival factors Bfl-1 and Bcl-xL,
down-regulation of pro-apoptotic protein Bim, increased T cell proliferation
and differentiation into T memory cells.
PF 04518600 is a fully human Immunoglobulin G2 (IgG2) agonistic monoclonal
antibody (mAb) specific for human OX40 (CD134). By binding to OX40 on
activated tumor infiltrating T cells, PF 04518600 may reverse T cells* anergic
state, and enhance tumor immunity.
Utomilumab (PF-05082566) is a fully human IgG2 agonist monoclonal antibody
specific for human 4-1BB. The safety and tolerability of utomilumab is
currently being evaluated in a First-in-Patient Phase 1 study as a single agent
and in combination with rituximab (Study B1641001, IND 109,154). utomilumab
has been well tolerated (thus far up to 10 mg/kg) when administered as a single
agent every 4 weeks (Q4W). The safety profile of utomilumab either as single
agent or in combination with rituximab was manageable without occurrence of
treatment related life threatening (>Grade 4) adverse events (AEs).
In this clinical study, PF 04518600 as a monotherapy (Part A), and PF-04518600
in combination with utomilumab (Part B) will be evaluated for the treatment of
adult patients with select locally advanced or metastatic cancers who are
unresponsive to current available therapies, or for whom no standard therapy is
available.

Objectives for Part A1 Monotherapy Dose Escalation
Primary Objective:
* To assess safety, and tolerability at increasing dose levels of PF 04518600
in patients with selected advanced or metastatic solid tumors in order to
establish the MTD.
Secondary Objectives:
* To assess preliminary anti tumor clinical activity induced by PF 04518600 in
patients with selected advanced or metastatic solid tumors solid tumors.
* To characterize the single dose and multiple dose pharmacokinetics (PK) of PF
04518600 following intravenous (IV) administration.
* To evaluate the immunogenicity of PF-04518600 following IV administration.
* To characterize the degree of target engagement (TE) by PF-04518600 at
multiple doses by measuring unbound (free) cell surface OX40 in peripheral
blood.

Exploratory Objectives
* To assess the pharmacodynamic activity (immune modulatory effects) of
PF-04518600 in tumor tissue by measuring the number, distribution and phenotype
of tumor infiltrating lymphocytes (TILs).
* To explore the effect of PF-04518600 on the ribonucleic acid (RNA) expression
profile in tumor biopsy tissue.
* To explore the effect of PF 04518600 on the abundance of T cell clones and
diversity of the T cell repertoire in tumor biopsy tissue and peripheral blood.
* To explore the effect of PF-04518600 on the prevalence and diversity of tumor
antigenic epitopes in tumor biopsy tissue.
* To evaluate the effect of PF-04518600 on levels of cytokines, chemokines and
soluble OX40.

Objectives for Part A2 Monotherapy Dose Expansion
Primary Objectives:
* To establish the recommended phase 2 dose (RP2D) of PF 04518600 in patients
with selected advanced or metastatic HCC.
* To further characterize the safety and tolerability of PF 04518600 in
patients with selected advanced or metastatic HCC.
Secondary Objectives:
* To assess preliminary anti tumor clinical activity of PF 04518600 in patients
with selected advanced or metastatic HCC.
* To characterize the single dose and multiple dose PK of PF 04518600 following
IV administration.
* To evaluate the immunogenicity of PF-04518600 following IV administration

Exploratory Objectives
* To assess the pharmacodynamic activity (immune modulatory effects) of
PF-04518600 in tumor tissue by measuring the number, distribution and phenotype
of TILs.
* To explore the effect of PF-04518600 on the RNA expression profile in tumor
biopsy tissue.
* To explore the effect of PF 04518600 on the abundance of T cell clones and
diversity of the T cell repertoire in tumor biopsy tissue and peripheral blood.
* To explore the effect of PF-04518600 on the prevalence and diversity of tumor
antigenic epitopes in tumor biopsy tissue.
* To evaluate the effect of PF-04518600 on levels of cytokines, chemokines and
soluble OX40.
* To characterize the degree of TE by PF-04518600 at multiple doses by
measuring unbound (free) cell surface OX40 in peripheral blood.

Objectives for Part B1 Combination Therapy Dose Escalation
Primary Objective:
* To assess safety and tolerability at increasing dose levels of PF-04518600 in
combination with utomilumab in patients with selected advanced or metastatic
solid tumors and to estimate MTD of the combination.

Secondary Objectives
* To assess preliminary anti-tumor clinical activity of PF-04518600 in
combination with utomilumab.
* To characterize single and multiple dose pharmacokinetics of PF-04518600 and
utomilumab when given in combination.
* To evaluate immunogenicity of PF-04518600 and utomilumab when given in
combination.

Exploratory Objectives:
* To assess the pharmacodynamic activity (immune modulatory effects) of PF
04518600 in combination with utomilumab (PF-04518600 / utomilumab) in
peripheral blood as measured by expression of activation markers such as Ki67
and human leukocyte antigen-D related (HLA-DR) in T cells.
* To assess the pharmacodynamic activity of PF-04518600 / utomilumab in tumor
tissue by measuring the number, distribution and phenotype of TILs.
* To explore the effect of PF-04518600 / utomilumabon the RNA expression
profile in tumor biopsy tissue.
* To explore the effect of PF 04518600 / utomilumab on the abundance of T cell
clones and diversity of the T cell repertoire in tumor biopsy tissue and
peripheral blood.
* To explore the effect of PF-04518600 / utomilumab on the prevalence and
diversity of tumor antigenic epitopes in tumor biopsy tissue.
* To evaluate the effect of PF-04518600 / utomilumab on levels of serum
cytokines, chemokines, soluble OX40 and soluble 4-1BB.
* To characterize the degree of TE by PF-04518600 when dosed in combination
with PF 05082566 by measuring unbound (free) cell surface OX40 in peripheral
blood.
* To explore the potential for drug-drug interactions between PF-04518600 and
utomilumab.

Objectives for Part B2 Combination Therapy Dose Expansion
Primary Objective:
* To further assess safety and tolerability of PF-04518600 in combination with
utomilumab in patients with melanoma or NSCLC in order to establish RP2D for
the combination.

Secondary Objectives:
* To assess preliminary anti-tumor clinical activity of PF-04518600 in
combination with utomilumab.
* To characterize single and multiple dose pharmacokinetics of PF-04518600 and
utomilumab when given in combination.
* To evaluate immunogenicity of PF-04518600 and utomilumab when given in
combination.

Exploratory Objectives:
* To assess the pharmacodynamic activity (immune modulatory effects) of PF
04518600 in combination with utomilumab (PF-04518600 / utomilumab) in
peripheral blood as measured by expression of activation markers such as Ki67
and HLA-DR in T cells.
* To assess the pharmacodynamic activity of PF-04518600 / utomilumab in tumor
tissue by measuring the number, distribution and phenotype of TILs.
* To explore the effect of PF-04518600 / utomilumab on the RNA expression
profile in tumor biopsy tissue.
* To explore the effect of PF 04518600 / utomilumab on the abundance of T cell
clones and diversity of the T cell repertoire in tumor biopsy tissue and
peripheral blood.
* To explore the effect of PF-04518600 / utomilumab on the prevalence and
diversity of tumor antigenic epitopes in tumor biopsy tissue.
* To evaluate the effect of PF-04518600 / PF-05082566 on levels of serum
cytokines, chemokines, soluble OX40 and soluble 4-1BB.
* To characterize the degree of TE by PF-04518600 when dosed in combination
with PF-05082566 by measuring unbound (free) cell surface OX40 and 4-1BB in
peripheral blood.
* To explore the potential for drug-drug interactions between PF-04518600 and
utomilumab.

This is a Phase 1, open label, multi center, multiple dose, dose escalation,
safety, pharmacokinetic, and pharmacodynamic study of PF 04518600 monotherapy
in Part A, and PF-04518600 in combination with utomilumab in Part B. Each part
includes a dose escalation phase, and a dose expansion phase. A maximum of
approximately 210 patients are expected to be enrolled into the study.
All patients will complete up to 4 weeks of screening. Following the initial
dose(s), treatment with investigational product will continue until either
disease progression, by immune-related response evaluation criteria in solid
tumors (irRECIST), by patient refusal or unacceptable toxicity occurs, or end
of study. Patients will be allowed to stay on study, if the treating physician
feels that it is in the patient*s best interest in the case of radiological
progression, and the absence of clear clinical progression. A follow up visit
approximately 4 weeks after the last dose for adverse event (AE) and serious AE
(SAE) collection will be conducted. Late immune related responses will be
evaluated up to 98 days after the first dose(s) of cycle 1. Because atypical
tumor responses after growth of pre-existing lesions or appearance of new
lesions have been observed with immune checkpoint inhibitors, study B0601002
will assess tumor response based on both response evaluation criteria in solid
tumor (RECIST) and Immune-related Response Criteria Derived From RECIST v1.1
(irRECIST). Survival data will also be collected. The time on study can vary
depending on the observed toxicity and potential benefit an individual subject
derives. It*s estimated that patients will remain on treatment for
approximately 12-18 weeks, making total study duration approximately 20 26
weeks (exclusive of 2 year survival follow-up). Actual duration can be longer,
if a patient derives benefit from study treatment.
Part A Monotherapy
Part A1 Monotherapy Dose Escalation
Part A1 monotherapy dose escalation phase will enroll approximately 58 adult
patients with locally advanced or metastatic cancers hepatocellular carcinoma
(HCC), melanoma, clear cell renal cell carcinoma (RCC) or head and neck
squamous cell carcinoma (HNSCC). The actual number of patients enrolled will
depend on the observed safety and tolerability profile of PF 04518600, the
number of dose levels that will be tested and expanded to characterize the
pharmacodynamic or immunomodulatory (IM) effects, and the number of dose levels
required to identify the maximum tolerated dose (MTD) or optimal biological
dose (OBD). Six dose levels are proposed: 0.01, 0.1, 0.3, 1.5, 3.0 and 10.0
mg/kg. Each cohort will include an initial cohort of 2-4 patients that may be
expanded to approximately 10 patients. Approximately 3 patients enrolled in
Japan will be included for at least 2 dose levels.
A staggered start will be employed at all dose levels. A single patient will
be dosed and observed for 48 hours. If no safety concerns arise during this 48
hr period, a second patient will be enrolled into the same dose level cohort.
A modified toxicity probability interval (mTPI) method, targeting a dose
limiting toxicities (DLT) rate of 25% and an acceptable DLT interval (20%-30%)
7, will be utilized for dose escalation. If peripheral blood samples indicate
preliminary signs of immune modulation in the first 2-4 patients, the dose
level will be expanded for pharmacodynamic evaluation; these additional
patients will undergo mandatory pre treatment and on treatment biopsies. If the
Investigator judges the risk of certain on-treatment biopsies unacceptable for
the patient (eg, based on site of tumor, potential for complications
during/after procedure, etc.) the medical monitor must be consulted. Depending
on observed safety data and pharmacodynamic data, additional cohorts (lower,
intermediate or higher dose levels, up to maximum of 20 mg/kg) may also be
tested.

Part A2 Monotherapy Dose Expansion
Part A2 monotherapy dose expansion phase will randomize HCC patients 1:1 to
flat dose levels of either 30 mg (Arm 1) or 250 mg (Arm 2) of PF-04518600 given
every 2 weeks. Both doses were chosen based on data from Part A1. Each arm in
Part A2 will include approximately 20 HCC patients.
Based on emerging data from the 10 mg/kg cohort of Part A1, an additional flat
dose level of 800 mg PF-04518600 (approximately equivalent to 10 mg/kg), may be
added after initiation of enrollment into Arms 1 and 2.
Patients will undergo mandatory pre-treatment and on treatment biopsies as
specified in the Schedule of Activities. If the Investigator judges the risk of
certain on-treatment biopsies unacceptable for the patient (eg, based on site
of tumor, potential for complications during/after procedure, etc.) the medical
monitor must be consulted (see Section 1.4 Rationale for Pretreatment and
On-treatment Biopsies)

Part B Combination Therapy
Part B1 Combination Therapy Dose Escalation
Part B1, the combination therapy dose escalation phase, will enroll
approximately 53 patients. At least 6 patients must have been evaluated for
the 28 day DLT observation period at the 0.3 mg/kg dose level in Part A1
PF-04518600 (OX40 agonist) monotherapy before Part B1 can be initiated. Part
B1 will study sequential dose levels of PF 04518600 (0.1, 0.3, 1.0 and 3 mg/kg
with an option of 10 mg/kg pending data from Part A1) combined with either 20
mg or 100 mg of tomilumab (4-1BB agonist) in adult patients with non-small cell
lung cancer (NSCLC), HNSCC, melanoma, bladder, gastric or cervical cancer who
are unresponsive to currently available therapies or for whom no standard
therapy is available. The starting dose level will be 0.1 mg/kg of PF-04518600
and 20 mg of utomilumab, given no sooner than 30 minutes apart. Based on
emerging data in the 10 mg/kg Part A1 cohort, an optional cohort of 10 mg/kg
PF-04518600 in combination with 100 mg of utomilumab may be evaluated.
A modified toxicity probability interval (mTPI) method, targeting a dose
limiting toxicities (DLT) rate of 25% and an acceptable DLT interval (20%-30%)
7, will be utilized for dose escalation. If peripheral blood samples indicate
preliminary signs of immune modulation in the first 2-4 patients, the dose
level will be expanded for pharmacodynamic evaluation; these additional
patients will undergo mandatory pre-treatment and on treatment biopsies. In
case of intolerable toxicity at the starting dose level, the dose combination
will be reduced to 0.1 mg/kg of PF-04518600 and 10 mg of utomilumab.
Subsequent to the starting dose level, if dose de-escalation is recommended
after evaluation, intermediate dose levels between the previous dose
combination and current dose combination may be studied. Intrapatient dose
reductions are not permitted during the combination therapy with PF-04518600
and PF-05082566 unless, in discussion with the sponsor, a dose combination
level is deemed beyond the determined MTD for the combination.. Each dose
combination level will include an initial cohort of 2 4 patients that may be
expanded up to approximately 10 patients based on peripheral pharmacodynamic
assessments. To allow for better characterization of pharmacodynamic effects,
these additional patients will undergo mandatory pre treatment and on treatment
biopsies. If the Investigator judges the risk of certain on-treatment biopsies
unacceptable for the patient (eg, based on site of tumor, potential for
complications during/after procedure, etc.) the medical monitor must be
consulted. The safety of the first patient at each dose combination level will
be observed for 48 hours prior to enrolling subsequent patients.

Part B2 Combination Therapy Dose Expansion
Part B2 combination therapy dose expansion phase will further evaluate safety
and anti-tumor activity of PF-04518600/ utomilumab combination with a dosing
regimen selected based on results of Part B1 with flat dose equivalents of
PF-04518600. Part B2 will be divided into 2 arms: Arm 1 will enroll HNSCC
patients who have either: a) never been treated with anti- PD-L1 or PD-1 mAb or
b) those who 1) previously received prior anti-PD-L1 or anti-PD-1 mAb as most
recent therapy, and 2) did not have progressive disease as best overall
response on recent PD-L1/PD-1 therapy (ie stable disease * 3 months, PR, or
CR), and 3) who subsequently progressed, or are intolerant to PD-L1/PD-1 therapy

Arm 2 will enroll NSCLC patients who have a) previously received prior
anti-PD-L1 or anti-PD-1 mAb as most recent therapy, and 2) did not have
progressive disease as best overall response on recent PD-L1/ PD-1 therapy (ie
stable disease * 3 months, PR, or CR), and 3) who subsequently progressed, or
b) are intolerant to this therapy.

Part B2 will enroll up to 20 patients in each arm, and all patients will
undergo mandatory pre- and on-treatment tumor biopsies. If the Investigator
judges the risk of certain on-treatment biopsies unacceptable for the patient
(eg, based on site of tumor, potential for complications during/after
procedure, etc.) the medical monitor must be consulted.

Part A Monotherapy:
The dose of PF-04518600 will be administered intravenously (through a vein)
over a 60 minute period once every 2 weeks. If the drug is safely tolerated (no
unsafe or unacceptable effects on your body), the dose can be increased in
group A2.
The patient will have to provide blood samples (during all study visits except
day 2 of cyclus 1):
- to check for some viruses (HIV, hepatitis B and C)
- to evaluate the presence of chemicals produced by your immune cells
- for safety tests
- to measure the amount of PF-04518600 in your blood
- to measure antibodies against PF-04518600
- to measure how your body is responding to PF-04518600
- to see how your immune system is responding to PF-04518600
- to evaluate the heart enzymes troponinI and prohormone brain natriuretic
peptide (NTproBNP) for patients who have a history of adriamycin (doxorubicin)
treatment.
- for banked biospecimens
Also radiology scans and tumor biopsies will be taken to evaluate the tumour
(during screening, end of treatment visit and follow-up visit).

Part B Combinationtherapy:
De dose utomilumab will be administered every 4 week intravenously over a 60
minutes period. PF-04518600 will be administered no sooner than 30 minutes
after completion of the utomilumab infusion. If the combinationtherapy is
safely tolerated (no unsafe or unacceptable effects on your body), the dose can
be increased in group B2. The dose PF-04518600 will range from 0.01 mg/kg to
20 mg/kg and the dose utomilumab will have a range of 10 to 100 mg.
The patient will have to provide blood samples (during all study visits except
day 2 of cyclus 1):
- to check for some viruses (HIV, hepatitis B and C)
- to evaluate the presence of chemicals produced by your immune cells
- for safety tests
- to measure the amount of PF-04518600 in your blood
- to measure antibodies against PF-04518600
- to measure how your body is responding to PF-04518600
- to see how your immune system is responding to PF-04518600
- to evaluate the heart enzymes troponinI and prohormone brain natriuretic
peptide (NTproBNP) for patients who have a history of adriamycin (doxorubicin)
treatment.
- for banked biospecimens
Also radiology scans and tumor biopsies will be taken to evaluate the tumour
(during screening, end of treatment visit and follow-up visit).

There is no direct benefit for the patient but the study may provide useful
data for the future.
Disadvantages which should be taken into account with participation are:
* the extra time it takes you
* an additional hospitalization or prolonged hospitalization
* additional blood tests and other additional studies, which would not
otherwise be done
* keeping appointments
* possible side effects as described below:

This is the first study of PF-04518600 in patients, so there is only very
limited clinical experience to refer to.
As of the most recent safety update, a total of 58 patients have been treated
with PF-04518600, of these, 48 advanced cancer patients have been treated with
PF-04518600 alone Among the 48 advanced cancer patients treated with
PF-04518600 alone, the following adverse event was reported in at least 10% of
patients and considered related to PF-04518600 by the study doctor: *
Fatigue (tiredness) (27.1%)

In addition, the following adverse events were related to PF-04518600 by the
study doctor and reported in at least 1 patient but no more than 10% of
patients:
Abdominal pain, Eosinophil count increased (cells that protect the body against
infection and germs), Nausea, Abdominal pain upper Endocrine disorders, flushes
(hot flashes), Neutrophil count decreased (cells that protect the body against
infection and germs, Activated partial thromboplastin time (time it takes your
blood to clot may be affected), Feeling cold, Edema (abnormal amount of fluid
under the skin and in the body), Amylase increased (may be a sign of a
problem), Headache, Edema peripheral (abnormal amount of fluid under the skin
and in the lower parts of the body), Arthralgia (joint pain), Hyperuricemia
(high level of uric acid in the blood), Pain, Basophil count increased (cells
that protect the body against infection and germs), Hypophosphatemia
(abnormally low levels of phosphate in the blood), Pruritus (itchy skin), Blood
alkaline phosphatase increased (may be a sign of a problem with your bones),
Increased alanine aminotransferase (indicating adverse effect on liver),
Proteinuria (extra protein in the urine that could be a sign of kidney damage),
Blood bilirubin increased (indicating adverse effect on liver), Influenza
(Flu), Pruritus generalized (itchy all over body), Cardiac failure congestive
(heart unable to pump enough to meet the body*s needs), Influenza (Flu) like
illness, Rash generalized (rash that covers most of the body), Chills Infusion
related reaction, Rash maculo-papular (Skin rash with discolored and raised
areas), Constipation, Insomnia (difficulty sleeping or falling asleep), Visual
acuity reduced (ability to see clearly), Decreased appetite, International
normalized ratio increased (increased risk of bleeding), Vitiligo (skin losing
pigment/color), Dry mouth, Lipase increased (may be a sign of a problem),
Vomiting, Dyspnea (shortness of breath), Lymphopenia (low levels of cells that
protect the body against infection and germs), White blood cell count increased
(cells that protect the body against infection and germs), Electrocardiogram QT
prolonged (may result in your heart not beating in rhythm), Memory impairment,
Electrocardiogram Uwave abnormality (may result in your heart not beating in
rhythm), Myalgia (muscle pain)


During animal studies, the following side effects were noted: slight tremor and
pupil dilation. Because PF04518600 is an antibody (a type of protein), side
effects may occur by administration of an antibody. There may be an allergic
reaction with the following symptoms: fever, headache, nausea, vomiting, and
decrease in blood pressure. A low count of white blood cells (lymphocytes),
fatigue, flu-like symptoms, rash, joint pain, anemia (low red blood cell
count), nausea / vomiting, enlargement of spleen, and itching of the skin may
also occur. Other drugs similar to PF-04518600 have been linked to a
condition called Cytokine Release Syndrome, causing a variety of symptoms, such
as sudden onset of fever, chills, headache, nausea, or/and shortness of
breath. Whether or not there is a chance this can occur with PF-04518600 is
not known.

Possible side effects of PF-05082566:
As of the most recent safety update, a total of 167 patients have been treated
with PF-05082566, of these, 86 advanced cancer patients have been treated with
PF-05082566 alone.

Among the 86 advanced cancer patients treated with PF-05082566 alone, the
following adverse event was reported in at least 10% of patients and considered
related to PF 05082566 by the study doctor:
* Fatigue (tiredness) (11.6%)
The fatigue cases were generally mild to moderate with only 1 severe case
reported.

In addition, the following adverse events were related to PF-05082566 and
reported in at least 1 patient but no more than 10% of patients:
Abdominal pain, Hypertension (high blood pressure), Paresthesia (tingling or
numbness in hands or feet), Anemia (low number of red blood cells),
Hyponatremia (abnormally low levels of sodium in the blood), Paresthesia oral
(tingling or numbness in and around mouth), Back pain, Increased alanine
aminotransferase (indicating adverse effect on liver), Pneumonitis (damage to
the lungs that may cause difficulty breathing), Chills, Increased aspartate
aminotransferase (indicating adverse effect on liver), Pruritus (itchy skin),
Decreased appetite, Influenza (Flu) like illness, Pyrexia (fever), Diarrhea,
Insomnia (difficulty sleeping or falling asleep), Rash, Dizziness, Joint pain,
Skin rash with discolored and raised areas, Dyspnea (shortness of breath),
Muscle pain, Thrombocytopenia (low number of a type of blood cell (that helps
the blood to clot), Ear discomfort, Muscle spasm, Vaginal infection,
Enterocolitis (damage to the small and large bowel), Nausea, Vomiting, Eye
irritation, Oropharyngeal pain (throat pain), Weight Loss, Gout (swelling and
pain in the joints), Pain, Headache, Papule (small raised pimple)


During animal studies, the following side effects were noted: decrease in blood
platelets (which can increase your risk of bleeding or bruising), decrease in
red blood cells (which can make you feel tired), decrease in white blood cells
(which can increase your risk of getting an infection including upper
respiratory infection and pneumonia), vomiting, respiratory distress
(difficulty breathing), abnormalities in the tissue of the liver. Because
PF-05082566 is an antibody (a type of protein), side effects may occur by
administration of an antibody and cause an allergic reaction. Other drugs
similar to PF-05082566 have been linked to liver injury and a condition called
Cytokine Release Syndrome, causing a variety of symptoms, such as sudden onset
of fever, chills, headache, nausea, or/and shortness of breath. Whether or not
there is a chance these side effects can occur with PF-05082566 is not known.

Potential side effects of PF-04518600 plus PF-05082566:
As of the most recent safety update, a total of 10 advanced cancer patients
have been treated with PF-04518600 in combination with PF-05082566.

Among the 10 advanced cancer patients treated with PF-04518600 in combination
with PF-05082566, the following adverse event was reported in at least 10% of
patients and considered related to study drug(s) by the study doctor:
* Nausea (20%)

In addition, the following adverse events were related to study drug(s) by the
study doctor and reported in at least 1 patient but no more than 10% of
patients:
Diarrhea, Eosinophil count increased (cells that protect the body against
infection and germs), Flushing, Dysphonia (hoarseness), Fatigue (tired),
Vomiting