Merck and Pfizer Announce Discontinuation of Phase III JAVELIN Ovarian PARP 100 Trial in Previously Untreated Advanced Ovarian Cancer

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 discontinuation of the
ongoing Phase III JAVELIN Ovarian PARP 100 study evaluating the
efficacy and safety of avelumab in combination with chemotherapy
followed by maintenance therapy of avelumab in combination with
talazoparib,* a poly (ADP-ribose) polymerase (PARP) inhibitor, versus
an active comparator in treatment-naïve patients with locally
advanced or metastatic ovarian cancer (Stage III or Stage IV). The
alliance has notified health authorities and trial investigators of
the decision to discontinue the trial.

The decision was based on several emerging factors since the
trial's initiation, including the previously announced interim
results from JAVELIN Ovarian PARP 100. The alliance determined that
the degree of benefit observed with avelumab in frontline ovarian
cancer in that study does not support continuation of the JAVELIN
Ovarian PARP 100 trial in an unselected patient population and
emphasizes the need to better understand the role of immunotherapy in
ovarian cancer. Additional factors include the rapidly changing
treatment landscape and the approval of a PARP inhibitor in the
frontline maintenance setting. The decision to discontinue the
JAVELIN Ovarian PARP 100 trial was not made for safety reasons.

The alliance between Merck and Pfizer was the first to test an
immunotherapy in this indication, given the significant unmet need in
the treatment of ovarian cancer. Four out of five women with ovarian
cancer are diagnosed with disease that has spread to the lymph nodes
or to distant organs.1 Most women with advanced ovarian cancer
ultimately die within five years due to refractory, resistant or
recurrent disease.2,3

JAVELIN Ovarian PARP 100 (B9991030) is an open-label,
international, multi-center, randomized study designed to evaluate
the efficacy and safety of avelumab in combination with chemotherapy
followed by maintenance therapy of avelumab in combination with
talazoparib versus an active comparator in treatment-naïve patients
with locally advanced or metastatic ovarian cancer (Stage III or
Stage IV). The primary endpoint is progression-free survival (PFS) as
determined based on blinded independent central review (BICR)
assessment per RECIST v1.1.

The decision to discontinue the JAVELIN Ovarian PARP 100 trial
does not impact the currently approved indications for avelumab or
the remainder of the ongoing JAVELIN clinical development program.
The program involves at least 30 clinical programs and more than
9,000 patients evaluated across more than 15 different tumor types,
including breast, gastric/gastro-esophageal junction, and head and
neck cancers, Merkel cell carcinoma, non-small cell lung cancer, and
urothelial carcinoma.

*Avelumab and talazoparib are under clinical investigation for the
treatment of advanced ovarian cancer and have not been demonstrated
to be safe and effective for this use.

About Avelumab (BAVENCIO®)

Avelumab (BAVENCIO®) is a human anti-programmed death ligand-1
(PD-L1) antibody. Avelumab 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, avelumab has been shown to
release the suppression of the T cell-mediated antitumor immune
response in preclinical models.4-6 Avelumab has also been shown to
induce NK cell-mediated direct tumor cell lysis via
antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.6-8 In
November 2014, Merck and Pfizer announced a strategic alliance to
co-develop and co-commercialize avelumab.

BAVENCIO Approved Indications

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). BAVENCIO is currently approved for patients with MCC in more
than 45 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, the 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.

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

The special warnings and precautions for use for BAVENCIO include
infusion-related reactions and immune-related adverse reactions (such
as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis and
renal dysfunction, and other adverse reactions).

The SmPC list of the most common adverse reactions in patients
with solid tumors includes fatigue, nausea, diarrhea, decreased
appetite, constipation, infusion-related reactions, and weight loss
and vomiting.

Indication for talazoparib (TALZENNA®) from the US Prescribing
Information

TALZENNA is a poly (ADP-ribose) polymerase (PARP) inhibitor
indicated for the treatment of adult patients with deleterious or
suspected deleterious germline breast cancer susceptibility gene
(BRCA)-mutated (gBRCAm) human epidermal growth factor receptor 2
(HER2)-negative locally advanced or metastatic breast cancer. Select
patients for therapy based on an FDA-approved companion diagnostic
for TALZENNA.

Important Safety Information from the TALZENNA US Prescribing
Information

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML) have
been reported in patients who received TALZENNA. Overall, MDS/AML
have been reported in 2 out of 584 (0.3%) solid tumor patients
treated with TALZENNA in clinical studies.

Myelosuppression consisting of anemia, leukopenia/neutropenia,
and/or thrombocytopenia have been reported in patients treated with
TALZENNA. Grade >=3 anemia, neutropenia, and thrombocytopenia were
reported, respectively, in 39%, 21%, and 15% of patients receiving
TALZENNA. Discontinuation due to anemia, neutropenia, and
thrombocytopenia occurred, respectively, in 0.7%, 0.3%, and 0.3% of
patients.

Monitor complete blood counts for cytopenia at baseline and
monthly thereafter. Do not start TALZENNA until patients have
adequately recovered from hematological toxicity caused by previous
therapy. If hematological toxicity occurs, dose modifications (dosing
interruption with or without dose reduction) are recommended. With
respect to MDS/AML, for prolonged hematological toxicities, interrupt
TALZENNA and monitor blood counts weekly until recovery. If the
levels have not recovered after 4 weeks, refer the patient to a
hematologist for further investigations. If MDS/AML is confirmed,
discontinue TALZENNA.

TALZENNA can cause fetal harm when administered to pregnant women.
Advise women of reproductive potential to use effective contraception
during treatment and for at least 7 months following the last dose. A
pregnancy test is recommended for females of reproductive potential
prior to initiating TALZENNA treatment. Advise male patients with
female partners of reproductive potential or who are pregnant to use
effective contraception during treatment with TALZENNA and for at
least 4 months after receiving the last dose. Based on animal
studies, TALZENNA may impair fertility in males of reproductive
potential. Advise women not to breastfeed while taking TALZENNA and
for at least 1 month after receiving the last dose because of the
potential for serious adverse reactions in nursing infants.

The most common adverse reactions (>=20%) of any grade for
TALZENNA vs chemotherapy were fatigue (62% vs 50%), anemia (53% vs
18%), nausea (49% vs 47%), neutropenia (35% vs 43%), headache (33% vs
22%), thrombocytopenia (27% vs 7%), vomiting (25% vs 23%), alopecia
(25% vs 28%), diarrhea (22% vs 26%), and decreased appetite (21% vs
22%).

The most frequently reported Grade >=3 adverse reactions (>=5%)
for TALZENNA vs chemotherapy were anemia (39% vs 5%), neutropenia
(21% vs 36%), and thrombocytopenia (15% vs 2%).

The most common lab abnormalities (>=25%) for TALZENNA vs
chemotherapy were decreases in hemoglobin (90% vs 77%), leukocytes
(84% vs 73%), lymphocytes (76% vs 53%), neutrophils (68% vs 70%),
platelets (55% vs 29%), and calcium (28% vs 16%) and increases in
glucose (54% vs 51%), aspartate aminotransferase (37% vs 48%),
alkaline phosphatase (36% vs 34%), and alanine aminotransferase (33%
vs 37%).

Coadministration with P-gp inhibitors or BCRP inhibitors may
increase TALZENNA exposure. If coadministering with the P-gp
inhibitors amiodarone, carvedilol, clarithromycin, itraconazole, or
verapamil is unavoidable, reduce the TALZENNA dose to 0.75 mg once
daily. When the P-gp inhibitor is discontinued, increase the TALZENNA
dose (after 3-5 half-lives of the P-gp inhibitor) to the dose used
prior to the initiation of the P-gp inhibitor. When co-administering
TALZENNA with other known P-gp inhibitors or BCRP inhibitors, monitor
patients for potential increased adverse reactions.

For patients with moderate renal impairment, the recommended dose
of TALZENNA is 0.75 mg once daily. No dose adjustment is required
for patients with mild renal impairment. TALZENNA has not been
studied in patients with severe renal impairment or in patients
requiring hemodialysis.

TALZENNA has not been studied in patients with moderate or severe
hepatic impairment. No dose adjustment is required for patients with
mild hepatic impairment.

Please see full US Prescribing Information
(http://labeling.pfizer.com/ShowLabeling.aspx?id=11046) available at
http://www.TALZENNA.com.

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 avelumab, an anti-PD-L1 antibody
initially discovered and developed by Merck. The immuno-oncology
alliance is jointly developing and commercializing avelumab. The
alliance is focused on developing high-priority international
clinical programs to investigate avelumab as a monotherapy as well as
combination regimens, and is striving to find new ways to treat
cancer.

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About Merck

Merck, a leading science and technology company, operates across
healthcare, life science and performance materials. Around 52,000
employees work to make a positive difference to millions of people's
lives every day by creating more joyful and sustainable ways to live.
From advancing gene editing technologies and discovering unique ways
to treat the most challenging diseases to enabling the intelligence
of devices - Merck is everywhere. In 2018, Merck generated sales of
EUR 14.8 billion in 66 countries.

Scientific exploration and responsible entrepreneurship have been
key to Merck's technological and scientific advances. This is how
Merck has thrived since its founding in 1668. The founding family
remains the majority owner of the publicly listed company. Merck
holds the global rights to the Merck name and brand. The only
exceptions are the United States and Canada, where the business
sectors of Merck operate as EMD Serono in healthcare, MilliporeSigma
in life science, and EMD Performance Materials.

Pfizer Inc.: Working together for a healthier world®

At Pfizer, we apply science and our global resources to bring
therapies to people that extend and significantly improve their
lives. We strive to set the standard for quality, safety and value in
the discovery, development and manufacture of health care products.
Our global portfolio includes medicines and vaccines as well as many
of the world's best-known consumer health care products. Every day,
Pfizer colleagues work across developed and emerging markets to
advance wellness, prevention, treatments and cures that challenge the
most feared diseases of our time. Consistent with our responsibility
as one of the world's premier innovative biopharmaceutical companies,
we collaborate with health care providers, governments and local
communities to support and expand access to reliable, affordable
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to make a difference for all who rely on us. We routinely post
information that may be important to investors on our website at
www.pfizer.com. In addition, to learn more, please visit us on
www.pfizer.com and follow us on Twitter at @Pfizer and @Pfizer_News,
LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.

Pfizer Disclosure Notice

The information contained in this release is as of March 19, 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 avelumab
(BAVENCIO), the Merck-Pfizer Alliance involving avelumab, 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 avelumab; 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 in any
jurisdictions for any potential indications for avelumab, combination
therapies or talazoparib; whether and when regulatory authorities in
any jurisdictions where applications are pending or may be submitted
for avelumab, combination therapies or talazoparib 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, safety, manufacturing
processes and/or other matters that could affect the availability or
commercial potential of avelumab, combination therapies or
talazoparib; 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. SEER Cancer Stat Facts: Ovarian Cancer. National Cancer Institute.
Bethesda, MD, https://seer.cancer.gov/statfacts/html/ovary.html.
Accessed March 2019.
2. Ledermann, JA, Raja FA, Fotopoulou C, et al. Newly diagnosed and
relapsed epithelial ovarian carcinoma: ESMO Clinical Practice
Guidelines for diagnosis, treatment and follow-up. Ann Oncol.
2013; 24 (Supplement 6): vi24-vi32, doi:10.1093/annonc/mdt333.
3. Ozol, RJ. Challenges for chemotherapy in ovarian cancer. Ann
Oncol. 2006;17(5):v181-187.
4. Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the landscape
of cancer immunotherapy. Cancer Control. 2014;21(3):231-237.
5. 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.
6. 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.
7. Kohrt HE, Houot R, Marabelle A, et al. Combination strategies to
enhance antitumor ADCC. Immunotherapy. 2012;4(5):511-527.
8. Hamilton G, Rath B. Avelumab: combining immune checkpoint
inhibition and antibody-dependent cytotoxicity. Expert Opin Biol
Ther. 2017;17(4):515-523.

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Pfizer
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Investor Relations: +1-212-733-8160, ryan.crowe@pfizer.com

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