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- Two-year follow-up data on meaningful
durable response, overall survival (OS) and
progression-free survival (PFS) to be presented in
patients with metastatic Merkel cell carcinoma (mMCC), a rare and
aggressive type of skin cancer
CHICAGO, June 4, 2018 /CNW/ -
Merck and Pfizer today announced that updated efficacy and
safety data from the pivotal JAVELIN Merkel 200 trial of
BAVENCIO® (avelumab) in patients with metastatic Merkel
cell carcinoma (mMCC), will be presented as an oral abstract
session at the 54th American Society of Clinical
Oncology (ASCO) Annual Meeting on Monday,
June 4 from 10:12-10:24 a.m.
CDT in Chicago, IL. At this
two year follow-up update of the pivotal study, BAVENCIO continues
to demonstrate clinically meaningful durable responses and stable
rates of progression-free survival (PFS) and overall survival (OS)
from previous analyses in patients who responded to this treatment.
Clinical activity was observed across all patient subgroups,
irrespective of PD-L1 expression in tumor tissue or Merkel cell
polyomavirus status. The safety profile for BAVENCIO in this trial
has not changed with longer follow-up and remains consistent with
that observed in the overall JAVELIN clinical development
program.
"These efficacy and safety results build upon the data that
supported our FDA approval," said Luciano
Rossetti, M.D., Executive Vice President, Global Head of
Research & Development at the Biopharma business of Merck.
"Alongside our other data at ASCO, this two-year analysis is a
significant advance in our understanding of the utility of BAVENCIO
in MCC patients."
In JAVELIN Merkel 200 - an open-label, single-arm Phase II study
- patients with histologically confirmed mMCC whose disease had
progressed on or after chemotherapy administrated for distant
metastatic disease received BAVENCIO 10 mg/kg intravenously every
two weeks until disease progression or unacceptable toxicity.
Eighty-eight patients were followed for a median of 29.2 months
(range 24.8-38.1 months). The confirmed overall response rate (ORR)
of 33% (95% confidence interval [CI] 23.3-43.8; complete response
in 11.4%) remained unchanged from previous analyses reported at
both one year and 18 months. Responses remained ongoing in 19 of 29
patients who responded to treatment, including 12 patients whose
duration of response exceeded two years. Durable responses led to
stable rates of PFS (29% at 12 months, 29% at 18 months and 26% at
24 months). Median OS was 12.6 months (95% CI 7.5-17.1) and the
two-year OS rate was 36% (50% at 12 months and 39% at 18 months).
With a minimum follow-up of two years, no new safety signals were
identified for BAVENCIO and was consistent with prior reports.
Sixty-seven patients (76.1%) had a treatment related adverse event
(TRAE), 10 patients (11.4%) had a Grade 3 or less TRAE and 20
patients (22.7%) had an immune-related adverse event. No
treatment-related deaths occurred.
"These results represent a key milestone for patients with mMCC,
as chemotherapy has historically been the only treatment option for
this devastating disease," said Chris
Boshoff, M.D., Ph.D., Senior Vice President and Head of
Immuno-Oncology, Early Development and Translational Oncology,
Pfizer Global Product Development. "These data, alongside the
additional real-world data which are also being presented at ASCO,
strengthen our confidence in BAVENCIO as a treatment option for
this rare and aggressive skin cancer."
In addition to these updated JAVELIN Merkel 200 data, results
from a global expanded access program for BAVENCIO as a second-line
treatment for patients with mMCC will be presented. These data will
be presented during a poster session on Monday, June 4 from
1:15-4:45 p.m. CDT.
The alliance's JAVELIN clinical development program involves at
least 30 clinical programs, including seven Phase III trials, and
nearly 8,300 patients across more than 15 tumor types.
*BAVENCIO® (avelumab) was first approved in the US in
2017 by the US Food and Drug Administration (FDA) for the treatment
of adults and pediatric patients 12 years and older with metastatic
Merkel cell carcinoma (mMCC). In addition to the FDA accelerated
approval in mMCC, avelumab is also approved in the US under
accelerated approval for the treatment of patients with locally
advanced or metastatic urothelial carcinoma (UC) who have disease
progression during or following platinum-containing chemotherapy,
or who 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.
About JAVELIN Merkel 200
JAVELIN Merkel 200 is an international, multicenter, open-label,
single-arm Phase II study of BAVENCIO conducted in 88 patients with
metastatic MCC. Patients in this study were generally elderly
(median age was 72.5 years, range 33-88 years) and pre-treated,
with at least one line of chemotherapy (one [59.1%], two [29.5%] or
three or more [11.4%] previous treatments). Patients received
BAVENCIO 10 mg/kg intravenously once every two weeks. The
protocol-defined analysis set for efficacy and safety consisted of
all patients who received at least one dose of study treatment. The
cut-off date for the planned primary analysis was six months after
start of study treatment of the last patient. The primary endpoint
of the study was confirmed best overall response according to
RECIST v1.1 and assessed by an independent review committee.
Secondary endpoints were duration of response, PFS, OS, response
status by RECIST at six and 12 months, safety and tolerability,
pharmacokinetics, and immunogenicity of BAVENCIO.
About Avelumab
Avelumab 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.[2]-[4]
Avelumab has also been shown to induce NK cell-mediated direct
tumor cell lysis via antibody-dependent cell-mediated cytotoxicity
(ADCC) in
vitro.[4]-[6]
In November 2014, Merck and Pfizer
announced a strategic alliance to co-develop and co-commercialize
avelumab.
Approved Indications in the US
The 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.
Important Safety Information from the US FDA Approval
Label
The warnings and precautions for BAVENCIO include
immune-mediated adverse reactions (such as pneumonitis, hepatitis,
colitis, endocrinopathies, nephritis and renal dysfunction, and
other adverse reactions), infusion-related reactions and
embryo-fetal toxicity.
Common adverse reactions (reported in at least 20% of patients)
in patients treated with BAVENCIO for mMCC and patients with
locally advanced or mUC include fatigue, musculoskeletal pain,
diarrhea, nausea, infusion-related reaction, peripheral edema,
decreased appetite/hypophagia, urinary tract infection and
rash.
About the 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 and advancing Pfizer's PD-1 antibody. The
alliance is focused on developing high-priority international
clinical programs to investigate avelumab as a monotherapy as well
as in combination regimens, and is striving to find new ways to
treat cancer.
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- from biopharmaceutical therapies to treat cancer or multiple
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In 2017, Merck generated sales of € 15.3 billion in 66
countries.
Founded in 1668, Merck is the world's oldest pharmaceutical and
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the company operates as EMD Serono, MilliporeSigma and EMD
Performance Materials.
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Pfizer Disclosure Notice
The information contained in this release is as of June 4, 2018. 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, the Merck-Pfizer Alliance involving anti-PD-L1 and
anti-PD-1 therapies, 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 study commencement and completion dates and regulatory
submission 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 interim
data; the risk that clinical trial data are subject to differing
interpretations, and, even when we view data as sufficient to
support the safety and/or effectiveness of a product candidate,
regulatory authorities may not share our views and may require
additional data or may deny approval altogether; 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 potential indications for avelumab,
combination therapies or other product candidates; whether and when
regulatory authorities in any jurisdictions where applications are
pending or may be submitted for avelumab, combination therapies or
other product candidates 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 avelumab, 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, 2016, 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
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References
- Nghiem P. Two-year efficacy and safety update from JAVELIN
Merkel 200 part A: a phase 2 study of avelumab in metastatic Merkel
cell carcinoma progressed on chemotherapy. Abstract 9507. To be
presented at ASCO 2018, June 1-4,
2018. Chicago, IL.
- Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the
landscape of cancer immunotherapy. Cancer Control
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- Dahan R, Sega E, Engelhardt J, et al. FcγRs modulate the
anti-tumor activity of antibodies targeting the PD-1/PD-L1 axis.
Cancer Cell 2015;28(3):285-95.
- 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):1148-57.
- Kohrt HE, Houot R, Marabelle A, et al. Combination strategies
to enhance antitumor ADCC. Immunotherapy 2012;4(5):511-27.
- Hamilton G, Rath B. Avelumab: combining immune checkpoint
inhibition and antibody-dependent cytotoxicity. Expert Opin Biol
Ther 2017;17(4):515-23.
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SOURCE Merck