European Commission Approves BAVENCIO® (avelumab) Plus Axitinib Combination for First-Line Treatment of Patients With Advanced Renal Cell Carcinoma

Not intended for US, Canada and UK-based media

-- EU approval based on JAVELIN Renal 101 trial results
demonstrating significant improvement in progression-free survival
with BAVENCIO in combination with axitinib compared with sunitinib

-- Combination regimen approved across all IMDC prognostic risk
groups and irrespective of PD-L1 expression

Darmstadt, Germany, and New York (ots/PRNewswire) - Merck and
Pfizer Inc. (NYSE: PFE) today announced that the European Commission
(EC) has approved BAVENCIO® (avelumab) in combination with axitinib
for the first-line treatment of adult patients with advanced renal
cell carcinoma (RCC). The approval was based on positive interim
results from the Phase III JAVELIN Renal 101 study, which
demonstrated that BAVENCIO in combination with axitinib significantly
lowered risk of disease progression or death by 31% (HR: 0.69 [95%
CI: 0.574-0.825; p<0.0001]) and nearly doubled objective response
rate (ORR; 52.5% [95% CI: 47.7-57.2] vs. 27.3% [95% CI: 23.2-31.6])
compared with sunitinib in patients with advanced RCC regardless of
PD-L1 status. The study included patients across International
Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic
risk groups. Improvement in progression-free survival (PFS) was
observed across pre-specified subgroups in patients receiving the
treatment combination.1 Merck and Pfizer have a global strategic
alliance to jointly develop and commercialize BAVENCIO.

"There is a high incidence of kidney cancer in Europe, and for the
most common type, renal cell carcinoma, we continue to need
additional treatment options, particularly for patients with advanced
disease, where outcomes are poorest," said Professor James Larkin,
Consultant Medical Oncologist at The Royal Marsden NHS Foundation
Trust and Professor at the Institute of Cancer Research (ICR). "We've
seen a demonstrated efficacy benefit and safety and tolerability
profile for avelumab in combination with axitinib across all
prognostic risk groups in patients with advanced renal cell
carcinoma, so today's approval in Europe brings an important option
that can help healthcare professionals optimize treatment strategies
across risk stratification."

In 2018, an estimated 136,500 new cases of kidney cancer were
diagnosed in Europe, and approximately 54,700 people died from the
disease.2 Many patients living with advanced RCC do not go on to
receive additional treatment after first-line therapy,3,4 for reasons
that may include poor performance status or adverse events from their
initial treatment.3,5,6 The five-year survival rate for patients with
advanced RCC is approximately 12%.7

"This first European approval of an anti-PD-L1 as part of a
combination treatment for advanced renal cell carcinoma builds on our
commitment to bringing innovative treatment options to patients with
hard-to-treat cancers through our extensive JAVELIN clinical trial
program," said Rehan Verjee, Global Head of Innovative Medicine
Franchises for the Biopharma business of Merck. "RCC is the most
common form of kidney cancer, accounting for 90% of diagnoses. We are
now working to make BAVENCIO in combination with axitinib available
for patients with advanced renal cell carcinoma as quickly as
possible."

"The European Commission approval of BAVENCIO in combination with
axitinib has the potential to bring even more patients with advanced
renal cell carcinoma a new first-line treatment, and it allows us to
continue to deliver on our more than decade-long passion to do more
for patients with kidney cancer," said Andy Schmeltz, Global
President, Pfizer Oncology. "We thank all of the researchers,
doctors, advocates, patients and their families who helped get us
here today, and we will continue in our fight against this advanced
cancer."

The EC's decision follows the U.S. Food and Drug Administration
(FDA) approval of BAVENCIO in combination with axitinib for the
first-line treatment of patients with advanced RCC in May 2019. A
supplemental application for BAVENCIO in combination with axitinib in
unresectable or metastatic RCC was submitted in Japan in January
2019.

Additionally, with this approval, the posology section of the
Summary of Product Characteristics for BAVENCIO has been updated. The
recommended dose of BAVENCIO as monotherapy is 800 mg administered
intravenously over 60 minutes every 2 weeks. Administration of
BAVENCIO should continue according to the recommended schedule until
disease progression or unacceptable toxicity. The recommended dose of
BAVENCIO in combination with axitinib is 800 mg administered
intravenously over 60 minutes every 2 weeks and axitinib 5 mg orally
taken twice daily (12 hours apart) with or without food until disease
progression or unacceptable toxicity.1

Data from JAVELIN Renal 101 Study Supporting Approval

This approval was based on interim data from the Phase III JAVELIN
Renal 101 study, a randomized, multicenter, open-label study of
BAVENCIO in combination with axitinib in 886 patients with untreated
advanced or metastatic RCC with a clear cell component. The study
included patients across risk groups (International Metastatic Renal
Cell Carcinoma Database Consortium [IMDC]: 21% favorable, 62%
intermediate and 16% poor; Memorial Sloan Kettering Cancer Center
[MSKCC]: 22% favorable, 65% intermediate and 11% poor). The primary
efficacy endpoints were progression-free survival (PFS) as assessed
by a Blinded Independent Central Review (BICR) using RECIST v1.1 and
overall survival (OS) in the first-line treatment of patients with
advanced RCC who have PD-L1-positive tumors (PD-L1 expression level
>1%). PFS based on BICR assessment per RECIST v1.1 and OS
irrespective of PD-L1 expression, objective response (OR), time to
response (TTR), duration of response (DOR) and safety are included as
secondary endpoints. The study is continuing for OS.

In the analysis, BAVENCIO in combination with axitinib
significantly improved median PFS compared with sunitinib by more
than five months in patients irrespective of PD-L1 expression (13.3
months [95% CI: 11.1-15.3] vs. 8.0 months [95% CI: 6.7-9.8]). With a
median follow-up for OS of 19 months, data for the trial's other
endpoint of OS were immature, with 27% of deaths, and the trial is
continuing as planned. The hazard ratio for OS in patients treated
with BAVENCIO in combination with axitinib compared with sunitinib
was 0.80 (95% CI: 0.616, 1.027) at the interim analysis.

The most common adverse reactions were diarrhea (62.8%),
hypertension (49.3%), fatigue (42.9%), nausea (33.5%), dysphonia
(32.7%), decreased appetite (26.0%), hypothyroidism (25.2%), cough
(23.7%), headache (21.3%), dyspnea (20.9%), and arthralgia (20.9%).

About the JAVELIN Clinical Development Program

The clinical development program for avelumab, known as JAVELIN,
involves at least 30 clinical programs and more than 10,000 patients
evaluated across more than 15 different tumor types. In addition to
RCC, these tumor types include gastric/gastro-esophageal junction
cancer, head and neck cancer, Merkel cell carcinoma, non-small cell
lung cancer and urothelial carcinoma.

About BAVENCIO® (avelumab)

BAVENCIO is a human anti-programmed death ligand-1 (PD-L1)
antibody. BAVENCIO has been shown in preclinical models to engage
both the adaptive and innate immune functions. By blocking the
interaction of PD-L1 with PD-1 receptors, BAVENCIO has been shown to
release the suppression of the T cell-mediated antitumor immune
response in preclinical models.8-10 In November 2014, Merck and
Pfizer announced a strategic alliance to co-develop and
co-commercialize BAVENCIO.

BAVENCIO Approved Indications

The European Commission has authorized the use of BAVENCIO in
combination with axitinib for the first-line treatment of adult
patients with advanced renal cell carcinoma (RCC). In September 2017,
the European Commission granted conditional marketing authorization
for BAVENCIO as a monotherapy for the treatment of adult patients
with metastatic Merkel cell carcinoma (MCC).

In the US, BAVENCIO in combination with axitinib is indicated for
the first-line treatment of patients with advanced renal cell
carcinoma (RCC). Additionally, the US Food and Drug Administration
(FDA) granted accelerated approval for avelumab (BAVENCIO®) for the
treatment of (i) adults and pediatric patients 12 years and older
with metastatic Merkel cell carcinoma (mMCC) and (ii) patients with
locally advanced or metastatic urothelial carcinoma (mUC) who have
disease progression during or following platinum-containing
chemotherapy, or have disease progression within 12 months of
neoadjuvant or adjuvant treatment with platinum-containing
chemotherapy. These indications are approved under accelerated
approval based on tumor response rate and duration of response.
Continued approval for these indications may be contingent upon
verification and description of clinical benefit in confirmatory
trials.

BAVENCIO is currently approved for patients with MCC in 50
countries globally, with the majority of these approvals in a broad
indication that is not limited to a specific line of treatment.

BAVENCIO Safety Profile from the EU Summary of Product
Characteristics (SmPC)

The special warnings and precautions for use for BAVENCIO
monotherapy include infusion-related reactions, as well as
immune-related adverse reactions that include pneumonitis and
hepatitis (including fatal cases), colitis, pancreatitis (including
fatal cases), myocarditis (including fatal cases), endocrinopathies,
nephritis and renal dysfunction, and other immune-related adverse
reactions. The special warnings and precautions for use for BAVENCIO
in combination with axitinib include hepatotoxicity.

The SmPC list of the most common adverse reactions with BAVENCIO
monotherapy in patients with solid tumors includes fatigue, nausea,
diarrhea, decreased appetite, constipation, infusion-related
reactions, weight decreased and vomiting. The list of most common
adverse reactions with BAVENCIO in combination with axitinib includes
diarrhea, hypertension, fatigue, nausea, dysphonia, decreased
appetite, hypothyroidism, cough, headache, dyspnea, and arthralgia.

About Merck-Pfizer Alliance

Immuno-oncology is a top priority for Merck and Pfizer. The global
strategic alliance between Merck and Pfizer enables the companies to
benefit from each other's strengths and capabilities and further
explore the therapeutic potential of BAVENCIO, an anti-PD-L1 antibody
initially discovered and developed by Merck. The immuno-oncology
alliance is jointly developing and commercializing BAVENCIO. The
alliance is focused on developing high-priority international
clinical programs to investigate BAVENCIO as a monotherapy as well as
combination regimens, and is striving to find new ways to treat
cancer.

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Pfizer Disclosure Notice

The information contained in this release is as of October 28,
2019. 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 BAVENCIO
(avelumab), including a new indication approved in the European Union
for BAVENCIO in combination with axitinib for the treatment of
patients with advanced renal cell carcinoma, the alliance between
Merck and Pfizer involving BAVENCIO 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, uncertainties
regarding the commercial success of BAVENCIO and axitinib; the
uncertainties inherent in research and development, including the
ability to meet anticipated clinical endpoints, commencement and/or
completion dates for our clinical trials, regulatory submission
dates, regulatory approval dates and/or launch dates, as well as the
possibility of unfavorable new clinical data and further analyses of
existing clinical data; risks associated with interim data; the risk
that clinical trial data are subject to differing interpretations and
assessments by regulatory authorities; whether regulatory authorities
will be satisfied with the design of and results from our clinical
studies; whether and when any drug applications may be filed for
BAVENCIO in combination with axitinib in any other jurisdictions or
in any jurisdictions for any other potential indications for BAVENCIO
or combination therapies; whether and when the pending application in
Japan for BAVENCIO in combination with axitinib may be approved and
whether and when regulatory authorities in any jurisdictions where
any other applications are pending or may be submitted for BAVENCIO
or combination therapies, including BAVENCIO in combination with
axitinib may approve any such applications, which will depend on
myriad factors, including making a determination as to whether the
product's benefits outweigh its known risks and determination of the
product's efficacy, and, if approved, whether they will be
commercially successful; decisions by regulatory authorities
impacting labeling, manufacturing processes, safety and/or other
matters that could affect the availability or commercial potential of
BAVENCIO or combination therapies, including BAVENCIO in combination
with axitinib; 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, 2018, 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.

References

1. BAVENCIO® (avelumab) EU SmPC. Available from:
http://www.ema.europa.eu/ema/. Accessed October 2019.
2. Ferlay J, Colombet M, Soerjomataram I, et al. Cancer incidence
and mortality patterns in Europe: Estimates for 40 countries and
25 major cancers in 2018. Eur J Cancer. 2018;103:356-387.
3. Eggers H, Ivanyi P, Hornig M, Grünwald V. Predictive factors for
second-line therapy in metastatic renal cell carcinoma: a
retrospective analysis. J Kidney Cancer VHL. 2017;4(1):8-15.
4. Motzer R, et al. Nivolumab plus Ipilimumab versus Sunitinib in
Advanced Renal-Cell Carcinoma. The New England Journal of
Medicine. 2018;378:1277-1290.
5. Eichelberg C, Vervenne WL, De Santis M, et al. SWITCH: A
randomised, sequential, open-label study to evaluate the efficacy
and safety of sorafenib-sunitinib versus sunitinib-sorafenib in
the treatment of metastatic renal cell cancer. Eur Urol.
2015;68;837-847.
6. Motzer RJ, Barrios CH, Kim TM, et al. Phase II randomized trial
comparing sequential first-line everolimus and second-line
sunitinib versus first-line sunitinib and second-line everolimus
in patients with metastatic renal cell carcinoma. J Clin Oncol.
2014;32:2765-2772.
7. Ridge C, Pua B, Madoff D. Epidemiology and staging of renal cell
carcinoma. Semin Intervent Radiol. 2014;31(1):3-8.
8. Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the
landscape of cancer immunotherapy. Cancer Control.
2014;21(3):231-237.
9. Dahan R, Sega E, Engelhardt J, et al. Fc?Rs modulate the
anti-tumor activity of antibodies targeting the PD-1/PD-L1 axis.
Cancer Cell. 2015;28(3):285-295.
10. Boyerinas B, Jochems C, Fantini M, et al. Antibody-dependent
cellular cytotoxicity activity of a novel anti-PD-L1 antibody
avelumab (MSB0010718C) on human tumor cells. Cancer Immunol Res.
2015;3(10):1148-1157.

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