Abstracts highlight data on BAVENCIO as a monotherapy and in combination in multiple advanced cancers

Not intended for US, Canada and UK-based media

Darmstadt, Germany, and New York (ots/PRNewswire) - Merck and
Pfizer Inc. (NYSE: PFE) today announced the presentation of multiple
analyses from the JAVELIN clinical development program assessing
BAVENCIO® (avelumab) alone or as part of combination regimens for the
treatment of advanced cancers, including renal cell carcinoma (RCC),
metastatic Merkel cell carcinoma (mMCC) and some other solid tumors
at the European Society for Medical Oncology (ESMO) Congress 2019 in
Barcelona, Spain.

"These data at ESMO underscore the clinical activity of treatment
with BAVENCIO across multiple tumor types and patient populations,"
said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology,
Pfizer Global Product Development. "Furthermore, these presentations
demonstrate our commitment to identifying the patients most likely to
benefit from this immunotherapy as a single agent, or in combination
approaches."

"The immunotherapy era has led to vast progress in the treatment
of cancer, yet we know that many patients with advanced or aggressive
cancers still need additional treatment options," said Luciano
Rossetti, M.D., Executive Vice President, Head of Global Research &
Development at the Biopharma business of Merck. "We are committed to
continued research of BAVENCIO as we seek to further advance
treatment options for patients with certain cancers."

Data to be presented at ESMO include three subgroup analyses of
the Phase III JAVELIN Renal 101 study (NCT02684006), a randomized,
multicenter, open-label study of BAVENCIO in combination with
axitinib in 886 patients with untreated advanced RCC from patients
across all International Metastatic RCC Database Consortium (IMDC)
risk groups. This study, results of which were published in The New
England Journal of Medicine in February 2019, demonstrated that
BAVENCIO in combination with axitinib significantly improved
progression-free survival (PFS) compared with sunitinib in patients
with advanced RCC, with a generally acceptable safety tolerability
profile, including serious adverse events.1

Results from new analyses of JAVELIN Renal 101 being presented at
ESMO, which assessed the effect of BAVENCIO in combination with
axitinib in subgroups including patients who did not undergo
cytoreductive nephrectomy, patients with sarcomatoid histology, and
Japanese patients, are consistent with findings from the overall
JAVELIN Renal 101 study population and provide a better understanding
of the combination in a broad range of patients with advanced RCC. In
May 2019, the U.S. Food and Drug Administration (FDA) approved
BAVENCIO in combination with axitinib for the first-line treatment of
patients with advanced RCC.2 The Committee for Medicinal Products for
Human Use (CHMP) of the European Medicines Agency (EMA) adopted a
positive opinion recommending approval of BAVENCIO in combination
with axitinib for the first-line treatment of adult patients with
advanced RCC in September 2019.

Presentation #908PD: Phase III JAVELIN Renal 101 Study Subgroup
Analysis of Patients with Advanced RCC who did not Undergo Upfront
Cytoreductive Nephrectomy

- Sunday, September 29, 15:20 - 15:20: Pamplona Auditorium (Hall 2)

A post-hoc analysis of JAVELIN Renal 101 evaluated patients with
advanced RCC who did not undergo prior surgery to remove as much of
the visible tumors on the kidneys as possible (cytoreductive
nephrectomy), which comprised 20.2% of participants in the study. The
findings showed that patients with advanced RCC treated with BAVENCIO
in combination with axitinib who did not undergo an upfront
cytoreductive nephrectomy experienced greater shrinkage of the
primary renal tumor versus sunitinib (>=30% shrinkage for best
percent change in renal target lesions from baseline in 34.5% versus
9.7%, respectively).3 The majority of patients with advanced RCC
undergo nephrectomy before starting systemic treatment,4 and those
who do undergo nephrectomy may experience complications or delays in
treatment.5 These results are the first of their kind to report the
efficacy of an immunotherapy plus a tyrosine kinase inhibitor in
patients with advanced RCC when there is still a primary tumor
present.3

Presentation #910PD: Phase III JAVELIN Renal 101 Study Subgroup
Analysis of Patients with Advanced RCC with Sarcomatoid Histology

- Sunday, September 29, 15:20 - 15:20: Pamplona Auditorium (Hall 2)

A post-hoc analysis of JAVELIN Renal 101 in patients with advanced
RCC with sarcomatoid histology, an aggressive subtype of RCC6 that
carries the worst prognosis for patients with renal tumors,7,8
included 12.2% of participants in the trial. The results presented at
ESMO showed that BAVENCIO plus axitinib improved PFS and objective
response rate (ORR) versus sunitinib in patients with advanced RCC
with sarcomatoid histology (median PFS: 7.0 months versus 4.0 months,
HR 0.57 [95% CI, 0.325-1.003]; median ORR: 46.8% versus 21.3%). These
findings provide insight into the biology of sarcomatoid histology
and treatment with this immunotherapy in this subgroup of patients.9

Presentation #956P: Phase III JAVELIN Renal 101 Study Subgroup
Analysis of Japanese Patients with Advanced RCC

- Monday, September 30, 12:20 - 12:20: Poster Area (Hall 4)

An analysis assessing the efficacy and safety of Japanese patients
with advanced RCC (n=67) in JAVELIN Renal 101 study showed that
BAVENCIO in combination with axitinib improved median PFS compared to
sunitinib in Japanese patients with advanced RCC regardless of PD-L1
expression (16.6 months versus 11.2 months, respectively; HR, 0.66;
[95% CI, 0.30-1.46]). Common treatment-emergent adverse events (grade
>=3) in each arm included hand-foot syndrome (9% versus 9%),
hypertension (30% versus 18%), and platelet count decreased (0%
versus 32%).10 A supplemental application for BAVENCIO in combination
with axitinib in unresectable or metastatic RCC was submitted in
Japan in January 2019.

Additional presentations at ESMO show the potential impact of
BAVENCIO as a monotherapy and as a component of novel combinations:

- An analysis of health-related quality of life (HRQoL) from the
Phase II JAVELIN Merkel 200 study, in which patients with mMCC, an
aggressive form of skin cancer with poor outcomes,11 treated with
BAVENCIO reported stable or improved HRQoL across various time
points (presentation #1320P).12
- Interim results from the Phase Ib JAVELIN IL-12 study evaluating
BAVENCIO in combination with M9241, Merck's investigational IL-12
fusion protein containing an anti-DNA antibody, in patients with
solid tumors, which informed the recommended dosing for Phase II of
this study (presentation #1224P).13
- Post-hoc analyses from the JAVELIN Solid Tumor Phase I trial
(presentation #1493P)14 and Phase III JAVELIN Lung 200 study
(presentation #1492P)15 that further elucidate the effects of
BAVENCIO in patients with advanced non-small cell lung cancer.

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.16-18 BAVENCIO has also been shown to
induce NK cell-mediated direct tumor cell lysis via
antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.18-20
In November 2014, Merck and Pfizer announced a strategic alliance to
co-develop and co-commercialize BAVENCIO.

BAVENCIO Approved Indications

In September 2017, the European Commission granted conditional
marketing authorization for BAVENCIO® (avelumab) as a monotherapy for
the treatment of adult patients with metastatic Merkel cell carcinoma
(MCC). 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.

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 FDA granted accelerated
approval for 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.

Avelumab Important Safety Information from the US FDA-Approved
Label

The warnings and precautions for avelumab (BAVENCIO®) include
immune-mediated adverse reactions (such as pneumonitis and hepatitis,
colitis, endocrinopathies, nephritis and renal dysfunction and other
adverse reactions), infusion-related reactions, hepatotoxicity, major
adverse cardiovascular events (MACE), and embryo-fetal toxicity.

The most common adverse reactions (all grades, >= 20%) in patients
with metastatic Merkel cell carcinoma (MCC) were fatigue (50%),
musculoskeletal pain (32%), diarrhea (23%), nausea (22%),
infusion-related reaction (22%), rash (22%), decreased appetite
(20%), and peripheral edema (20%).

Selected treatment-emergent laboratory abnormalities (all grades,
>= 20%) in patients with metastatic MCC were lymphopenia (49%),
anemia (35%), increased aspartate aminotransferase (34%),
thrombocytopenia (27%), and increased alanine aminotransferase (20%).

The most common adverse reactions (all grades, >= 20%) in patients
with locally advanced or metastatic urothelial carcinoma (UC) were
fatigue (41%), infusion-related reaction (30%), musculoskeletal pain
(25%), nausea (24%), decreased appetite/hypophagia (21%), and urinary
tract infection (21%).

Selected laboratory abnormalities (Grades 3-4, >= 3%) in patients
with locally advanced or metastatic UC were hyponatremia (16%),
increased gamma-glutamyltransferase (12%), lymphopenia (11%),
hyperglycemia (9%), increased alkaline phosphatase (7%), anemia (6%),
increased lipase (6%), hyperkalemia (3%), and increased aspartate
aminotransferase (3%).

Fatal adverse reactions in patients occurred in 1.8% of patients
with advanced renal cell carcinoma (RCC) receiving BAVENCIO in
combination with axitinib. These included sudden cardiac death
(1.2%), stroke (0.2%), myocarditis (0.2%), and necrotizing
pancreatitis (0.2%).

The most common adverse reactions (all grades, >=20%) in patients
with advanced RCC receiving BAVENCIO in combination with axitinib (vs
sunitinib) were diarrhea (62% vs 48%), fatigue (53% vs 54%),
hypertension (50% vs 36%), musculoskeletal pain (40% vs 33%), nausea
(34% vs 39%), mucositis (34% vs 35%), palmar-plantar
erythrodysesthesia (33% vs 34%), dysphonia (31% vs 3.2%), decreased
appetite (26% vs 29%), hypothyroidism (25% vs 14%), rash (25% vs
16%), hepatotoxicity (24% vs 18%), cough (23% vs 19%), dyspnea (23%
vs 16%), abdominal pain (22% vs 19%), and headache (21% vs 16%).

Selected laboratory abnormalities (all grades, >=20%) worsening
from baseline in patients with advanced RCC receiving BAVENCIO in
combination with axitinib (vs sunitinib) were blood triglycerides
increased (71% vs 48%), blood creatinine increased (62% vs 68%),
blood cholesterol increased (57% vs 22%), alanine aminotransferase
increased (ALT) (50% vs 46%), aspartate aminotransferase increased
(AST) (47% vs 57%), blood sodium decreased (38% vs 37%), lipase
increased (37% vs 25%), blood potassium increased (35% vs 28%),
platelet count decreased (27% vs 80%), blood bilirubin increased (21%
vs 23%), and hemoglobin decreased (21% vs 65%).

Axitinib Important Safety Information from the US FDA-Approved
Label

In the study of advanced RCC after failure of one prior systemic
therapy, the warnings and precautions for axitinib include
hypertension, including hypertensive crisis, arterial and venous
thrombotic events, hemorrhagic events, cardiac failure,
gastrointestinal perforation and fistula, hypothyroidism, wound
healing complications, reversible posterior leukoencephalopathy
syndrome (RPLS), proteinuria, liver enzyme elevation, hepatic
impairment and fetal harm during pregnancy.

Common adverse events (reported in at least 20% of patients) in
patients receiving axitinib were diarrhea, hypertension, fatigue,
decreased appetite, nausea, dysphonia, hand-foot syndrome, weight
decreased, vomiting, asthenia and constipation.

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 September 27,
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 U.S. 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 and uncertainties regarding whether the other primary
endpoint of JAVELIN Renal 101 will be met; 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 applications in the European Union and 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. Motzer R, et al. Avelumab plus axitinib versus sunitinib for
advanced renal-cell carcinoma. N Engl J Med 2019; 380:1103-1115
2. BAVENCIO Prescribing Information. Rockland, MA: EMD Serono Inc.;
2019.
3. Albiges L, et al. Primary renal tumour shrinkage in patients
(pts) who did not undergo upfront cytoreductive nephrectomy
(uCN): subgroup analysis from the phase 3 JAVELIN Renal 101 trial
of first-line avelumab + axitinib (A + Ax) vs sunitinib (S) for
advanced renal cell carcinoma (aRCC). Annals of Oncology. 2019.
TBD.
4. Culp S. Cytoreductive nephrectomy and its role in the present-day
period of targeted therapy. Ther Adv Urol. 2015;7(5):275-285.
5. Silberstein J, et al. Systemic classification and prediction of
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6. Pichler, Renate et al. "Renal Cell Carcinoma with Sarcomatoid
Features: Finally New Therapeutic Hope?" Cancers. 2019;11(3):422.
7. Al-Juhaishi, T et al. "Survival outcomes in sarcomatoid renal
cell carcinoma." Journal of Clinical Oncology. 2018;36:15_suppl
8. American Cancer Society. Survival Rates for Kidney Cancer https:/
/amp.cancer.org/cancer/kidney-cancer/detection-diagnosis-staging/
survival-rates.html. Accessed September 2019.
9. Choueiri T, et al. Efficacy and biomarker analysis of patients
(pts) with advanced renal cell carcinoma (aRCC) with sarcomatoid
histology (sRCC): subgroup analysis from the phase 3 JAVELIN
Renal 101 trial of first-line avelumab plus axitinib (A+ Ax) vs
sunitinib (S). Annals of Oncology. 2019. TBD.
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vs sunitinib as first-line treatment for advanced renal cell
carcinoma: JAVELIN Renal 101 Japanese subgroup analysis. Annals
of Oncology. 2019. TBD.
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with metastatic Merkel cell carcinoma receiving second-line or
later avelumab treatment: 36-month follow up data. Annals of
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13. Strauss J, et al. Phase 1b, open-label, dose-escalation study of
M9241 (NHS-IL12) plus avelumab in patients (pts) with advanced
solid tumors. Annals of Oncology. 2019. TBD.
14. Hrinczenko B, et al. Long-term avelumab treatment in patients
with advanced non-small cell lung cancer (NSCLC): post hoc
analyses from JAVELIN Solid Tumor. Annals of Oncology. 2019. TBD.
15. Barlesi F, et al. Assessing the impact of subsequent checkpoint
inhibitor (CPI) treatment on overall survival: post hoc analyses
from the phase 3 JAVELIN Lung 200 study of avelumab vs docetaxel
in platinum-treated locally advanced/metastatic non-small cell
lung cancer (NSCLC). Annals of Oncology. 2019. TBD.
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anti-tumor activity of antibodies targeting the PD-1/PD-L1 axis.
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