Two Year Update of Pivotal JAVELIN Merkel 200 Trial Shows Continued Durable Responses with BAVENCIO(R) (avelumab)
Two Year Update of Pivotal JAVELIN Merkel 200 Trial Shows Continued Durable Responses with BAVENCIO(R) (avelumab)
PR73844
CHICAGO, June 4, 2018 /PRNewswire=KYODO JBN/ --
Not intended for US, Canada and UK-based media
- 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
Merck and Pfizer today announced that updated efficacy and safety data from
the pivotal JAVELIN Merkel 200 trial of BAVENCIO(R) (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(R) (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(R)) 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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develop technologies that improve and enhance life - from biopharmaceutical
therapies to treat cancer or multiple sclerosis, cutting-edge systems for
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Founded in 1668, Merck is the world's oldest pharmaceutical and chemical
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corporate group. Merck, Darmstadt, Germany holds the global rights to the
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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
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clinical development plans, including their potential benefits, that involves
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References
1) 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.
2) Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the landscape of
cancer immunotherapy. Cancer Control 2014;21(3):231-7.
3) Dahan R, Sega E, Engelhardt J, et al. FcgammaRs modulate the anti-tumor
activity of antibodies targeting the PD-1/PD-L1 axis. Cancer Cell
2015;28(3):285-95.
4) 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.
5) Kohrt HE, Houot R, Marabelle A, et al. Combination strategies to enhance
antitumor ADCC. Immunotherapy 2012;4(5):511-27.
6) Hamilton G, Rath B. Avelumab: combining immune checkpoint inhibition and
antibody-dependent cytotoxicity. Expert Opin Biol Ther 2017;17(4):515-23.
Contacts
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+1-212-733-8160
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SOURCE: Merck
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