Pfizer Presents Data from Phase 1b Trial Investigating Utomilumab (a 4-1BB agonist) in Combination with a Checkpoint Inhibitor

NEW YORK–(BUSINESS WIRE)– Pfizer Inc. (NYSE:PFE) today announced results from a Phase 1b trial of
Pfizer’s investigational immunotherapy agent utomilumab (the proposed
non-proprietary name for PF-05082566), a 4-1BB (also called CD137)
agonist, in combination with pembrolizumab, a PD-1 inhibitor, in
patients with advanced solid tumors. This is the first reported study of
a 4-1BB agonist combined with a checkpoint inhibitor. Encouraging safety
data from the study were shared today as an oral presentation at the 52^nd
Annual Meeting of the American Society of Clinical Oncology (ASCO) in
Chicago.

“While these are early data, the combination of utomilumab with
pembrolizumab demonstrates an encouraging safety profile and an early
indication of potential anti-tumor activity across solid tumors,” said
Anthony W. Tolcher, M.D., director of clinical research at South Texas
Accelerated Research Therapeutics (START) San Antonio. “We believe these
results warrant further investigation to confirm whether combining
utomilumab with a checkpoint inhibitor may amplify anti-tumor responses.”

Of the 23 patients enrolled in the trial, six had a confirmed complete
or partial response. The majority (four of six) of these responses
lasted at least six months, with two patients maintaining their response
for nearly one year at the time of data cut off. Treatment emergent
adverse events were generally mild and did not appear to increase with
higher doses of utomilumab, and no dose-limiting toxicity was reported.

“Pfizer believes that bringing the promise of immunotherapies for cancer
to more patients will occur through combining agents that work on
different pathways within the immune system,” said Chris Boshoff, vice
president and head of Early Development, Translational and
Immuno-Oncology for Pfizer Oncology. “We are exploring numerous
utomilumab combinations in order to better understand its potential role
in mobilizing the immune system against difficult-to-treat cancers.”

Pfizer is investigating utomilumab in both hematologic cancers and solid
tumors in several planned and ongoing trials. It is being evaluated as a
single agent across multiple tumors, in combination with rituximab in
lymphoma,¹ and in combination with other immunotherapies
(e.g., OX40 agonist [PF-04518600], anti-CCR4 [mogamulizumab] and
avelumab, an investigational fully human anti-PD-L1 IgG1 monoclonal
antibody being developed through an alliance between Merck KGaA,
Darmstadt, Germany, and Pfizer) in various solid tumors and
hematological malignancies.^2,3,4 The mogamulizumab/utomilumab
combination is a collaboration with Kyowa Hakko Kirin, Japan.³

About the Study

This Phase 1b dose-escalation study assessed overall safety,
pharmacokinetics, pharmacodynamics and anti-tumor activity of utomilumab
in combination with pembrolizumab in 23 patients with advanced solid
tumors (non-small cell lung, renal cell carcinoma, head and neck,
pancreatic, anaplastic thyroid, small-cell lung, colon, sarcoma, thymoma
and melanoma). The primary objective was to estimate the maximum
tolerated dose and select the recommended Phase 2 dose. Patients
received utomilumab (0.45 to 5.0 mg/kg) and pembrolizumab (2 mg/kg)
intravenously on day one of 21-day cycles. The number of cycles patients
have received across all doses ranged from two to 19, and five patients
remain on treatment (maximum dosing is 32 cycles).

The six confirmed responses included two complete responses in one
patient with small cell lung cancer and one patient with renal cell
carcinoma; partial responses were observed in one patient each with
renal cell carcinoma, non-small cell lung cancer, head and neck cancer
and anaplastic thyroid cancer. The most common treatment related adverse
events were rash, fatigue, itching, fever, decreased appetite and
nausea, with none reported as Grade 3 or 4. No patients discontinued due
to treatment related toxicity.

About Utomilumab

Utomilumab (PF-05082566) is a fully human monoclonal antibody (mAb)
agonist that selectively binds to 4-1BB (also called CD137), a protein
receptor expressed in many cancer-fighting T cells. When a 4-1BB agonist
binds to CD137, it has been observed to stimulate and increase the
number of T cells, which is believed to accelerate the immune response
to attack and kill cancer cells. In preclinical models, utomilumab has
shown anti-tumor activity by enhancing T cell mediated immune responses.^5,6,7
Utomilumab is being studied in combination with checkpoint inhibitors,
which act on another immune signaling pathway and are believed to work
by blocking signals from cancer cells which inhibit the host immune
system. This signal blockade may allow the host immune system to attack
cancer cells.

Learn more about how Pfizer Oncology is applying innovative approaches
in an effort to improve the outlook for people living with cancer at http://www.pfizer.com/research/therapeutic_areas/oncology.

About Pfizer Oncology

Pfizer Oncology is committed to the discovery, investigation and
development of innovative treatment options to improve the outlook for
patients worldwide. Our strong pipeline of biologics and small
molecules, one of the most robust in the industry, is studied with
precise focus on identifying and translating the best scientific
breakthroughs into clinical application for patients across a wide range
of cancers. By working collaboratively with academic institutions,
individual researchers, cooperative research groups, governments, and
licensing partners, Pfizer Oncology strives to cure or control cancer
with breakthrough medicines, to deliver the right drug for each patient
at the right time. For more information, please visit us at www.pfizer.com.
In addition, to learn more, follow us on Twitter at @Pfizer
and @Pfizer_News, LinkedIn, YouTube and
like us on Facebook at Facebook.com/Pfizer.

DISCLOSURE NOTICE: The information contained in this release
is as of June 4, 2016. Pfizer assumes no obligation to update
forward-looking statements contained in this release as the result of
new information or future events or developments.

This release contains forward-looking information about Pfizer’s
oncology portfolio, including utomilumab (PF-05082566), potential
combination therapies, the potential of immuno-oncology and clinical
development plans, including their potential benefits, that involves
substantial risks and uncertainties that could cause actual results to
differ materially from those expressed or implied by such statements.
Risks and uncertainties include, among other things, the uncertainties
inherent in research and development, including the ability to meet
anticipated clinical study commencement and completion dates as well as
the possibility of unfavorable study results, including unfavorable new
clinical data and additional analyses of existing clinical data; risks
associated with initial data, including the risk that the final results
of the Phase Ib for utomilumab and/or additional clinical trials may be
different from (including less favorable than) the initial data results
and may not support further clinical development; whether and when any
applications may be filed with regulatory authorities for utomilumab,
combination therapies or other product candidates; whether and when
regulatory authorities may approve any such applications, which will
depend on the assessment by such regulatory authorities of the
benefit-risk profile suggested by the totality of the efficacy and
safety information submitted; decisions by regulatory authorities
regarding labeling and other matters that could affect the availability
or commercial potential of utomilumab, combination therapies or other
product candidates; and competitive developments.

A further description of risks and uncertainties can be found in
Pfizer’s Annual Report on Form 10-K for the fiscal year ended December
31, 2015 and in its subsequent reports on Form 10-Q, including in the
sections thereof captioned « Risk Factors » and « Forward-Looking
Information and Factors That May Affect Future Results », as well as in
its subsequent reports on Form 8-K, all of which are filed with the U.S.
Securities and Exchange Commission and available at www.sec.gov
and www.pfizer.com.

¹ A Study of PF-05082566 As A Single Agent And In Combination
With Rituximab. Available at https://clinicaltrials.gov/ct2/show/NCT01307267?term=PF-05082566&rank=3.
Accessed April 25, 2016.

² A Study of Avelumab In Combination With Other Cancer
Immunotherapies In Advanced Malignancies (JAVELIN Medley). Available at https://clinicaltrials.gov/ct2/show/NCT02554812?term=PF-05082566&rank=4.
Accessed April 25, 2016.

³ A Study of PF-05082566 In Combination With Mogamulizumab In
Patients With Advanced Solid Tumors. Available at https://clinicaltrials.gov/ct2/show/NCT02444793?term=PF-05082566&rank=1.
Accessed April 25, 2016.

⁴ A Study of 4-1BB Agonist PF-05082566 Plus PD-1 Inhibitor
MK-3475 In Patients With Solid Tumors (B1641003/KEYNOTE-0036). Available
at https://clinicaltrials.gov/ct2/show/NCT02179918?term=PF-05082566&rank=2
Accessed April 25, 2016.

⁵ Fisher TS, Kamperschroer C, Oliphant T, et al. Targeting of
4-1BB by monoclonal antibody PF-05082566 enhances T-cell function and
promotes anti-tumor activity [published online ahead of print March 11,
2012]. Cancer Immunol Immunother. doi:10.1007/s00262-012-1237-1.

⁶ Westwood JA, Hunnam TC, Pegram HJ, et al. Routes of
delivery for CpG and anti-CD137 for the treatment of orthotopic kidney
tumors in mice. PLoS ONE. 2014; 9(5):1-10.

⁷ West H. Immune checkpoint inhibitors. JAMA Oncol.
2015;1(1):115. doi:10.1001/jamaoncol.2015.0137. Available at http://oncology.jamanetwork.com/article.aspx?articleid=2174768.
Accessed April 25, 2016.

View source version on businesswire.com: http://www.businesswire.com/news/home/20160604005038/en/