THOUSAND OAKS, Calif.,
Sept. 13, 2019 /PRNewswire/
-- Amgen (NASDAQ:AMGN) today announced the Phase 3 CANDOR
study evaluating KYPROLIS® (carfilzomib) in combination
with dexamethasone and DARZALEX® (daratumumab) (KdD)
compared to KYPROLIS and dexamethasone alone (Kd) met its primary
endpoint of progression-free survival (PFS). The regimen resulted
in a 37% reduction in the risk of progression or death in patients
with relapsed or refractory multiple myeloma treated with KdD
(HR=0.630; 95% CI: 0.464, 0.854; p=0.0014). The median PFS
for patients treated with Kd alone was 15.8 months, while the
median PFS for patients treated with KdD has not been reached by
the cut-off date.
"The potential to combine KYPROLIS with DARZALEX, two powerful
targeted agents, represents an additional therapeutic approach for
patients with relapsed or refractory multiple myeloma," said
David M. Reese, M.D., executive vice
president of Research and Development at Amgen. "The results from
the CANDOR study confirm the potential for KYPROLIS to be used in
combination with an anti-CD38 monoclonal antibody."
There was a higher frequency of adverse events reported in KdD,
a three-agent regimen, than in Kd, a two-agent regimen. The types
of observed adverse events were consistent with the known safety
profiles of the individual agents. The most frequently reported
treatment-emergent adverse events (greater than or equal to 20%) in
the KdD arm were thrombocytopenia, anemia, diarrhea, hypertension,
upper respiratory tract infection, fatigue and dyspnea.
"While treatment advances have improved outcomes for patients
with multiple myeloma, there remains a need for additional
therapeutic options for patients who have relapsed," said
Ajai Chari, M.D., associate
professor of medicine, the director of clinical research in the
Multiple Myeloma Program and the associate director of clinical
research, Mount Sinai Cancer Clinical Trials Office. "CANDOR
confirms in a large Phase 3 study the benefit for patients
demonstrated in the earlier Phase 1 study using the same
combination."
The CANDOR data will be submitted to a future medical meeting
and discussed with health authorities in preparation for
regulatory submissions.
About CANDOR
CANDOR, a randomized, open-label Phase 3
study of KYPROLIS, dexamethasone and DARZALEX (KdD) compared to
KYPROLIS and dexamethasone (Kd), has evaluated 466 relapsed or
refractory multiple myeloma patients who have received one to three
prior therapies. Patients were treated until disease progression.
The primary endpoint was PFS, and the key secondary endpoints were
overall response rate, minimal residual disease and overall
survival. PFS was defined as time from randomization until disease
progression or death from any cause.
In the first arm, patients received KYPROLIS twice weekly at 56
mg/m2 and dexamethasone in combination with
DARZALEX. In the second arm (control), patients received KYPROLIS
twice weekly at 56 mg/m2 and dexamethasone.
CANDOR was initiated as part of a collaboration with Janssen,
and under the terms of the agreement, Janssen co-funded the study.
For more information about this trial, please visit
www.clinicaltrials.gov under trial identification number
NCT03158688.
About Multiple Myeloma
Multiple myeloma is an
incurable blood cancer, characterized by a recurring pattern of
remission and relapse.1 It is a rare and
life-threatening disease that accounts for approximately one
percent of all cancers.2,3 Worldwide, approximately
160,000 people are diagnosed with multiple myeloma each year, and
106,000 patient deaths are reported on an annual
basis.2
About KYPROLIS® (carfilzomib)
Proteasomes
play an important role in cell function and growth by breaking down
proteins that are damaged or no longer
needed.4 KYPROLIS has been shown to block
proteasomes, leading to an excessive build-up of proteins within
cells.5 In some cells, KYPROLIS can cause cell
death, especially in myeloma cells because they are more likely to
contain a higher amount of abnormal proteins.4,5
Since its first approval in 2012, approximately 130,000 patients
worldwide have received KYPROLIS. KYPROLIS is approved in the U.S.
for the following:
- In combination with dexamethasone or with lenalidomide plus
dexamethasone for the treatment of patients with relapsed or
refractory multiple myeloma who have received one to three lines of
therapy
- As a single agent for the treatment of patients with relapsed
or refractory multiple myeloma who have received one or more lines
of therapy
KYPROLIS is also approved in Algeria, Argentina, Australia, Bahrain, Belarus, Brazil, Canada, Chile, Colombia, Ecuador, Egypt, European Union, Hong Kong, India, Israel, Japan, Jordan, Kuwait, Lebanon, Macao, Malaysia, Mexico, Morocco, New
Zealand, Oman, Philippines, Qatar, Russia, Saudi
Arabia, Singapore, S.
Korea, Switzerland, Taiwan, Thailand, Turkey and United
Arab Emirates.
Important U.S. KYPROLIS® (carfilzomib) Safety
Information
Cardiac Toxicities
- New onset or worsening of pre-existing cardiac failure (e.g.,
congestive heart failure, pulmonary edema, decreased ejection
fraction), restrictive cardiomyopathy, myocardial ischemia, and
myocardial infarction including fatalities have occurred following
administration of KYPROLIS. Some events occurred in patients with
normal baseline ventricular function. Death due to cardiac arrest
has occurred within one day of administration.
- Monitor patients for signs or symptoms of cardiac failure or
ischemia. Evaluate promptly if cardiac toxicity is suspected.
Withhold KYPROLIS for Grade 3 or 4 cardiac adverse events until
recovery, and consider whether to restart at 1 dose level reduction
based on a benefit/risk assessment.
- While adequate hydration is required prior to each dose in
Cycle 1, monitor all patients for evidence of volume overload,
especially patients at risk for cardiac failure. Adjust total fluid
intake as clinically appropriate.
- For patients ≥ 75 years, the risk of cardiac failure is
increased. Patients with New York Heart Association Class III and
IV heart failure, recent myocardial infarction, conduction
abnormalities, angina, or arrhythmias may be at greater risk for
cardiac complications and should have a comprehensive medical
assessment prior to starting treatment with KYPROLIS and remain
under close follow-up with fluid management.
Acute Renal Failure
- Cases of acute renal failure, including some fatal renal
failure events, and renal insufficiency adverse events (including
renal failure) have occurred. Acute renal failure was reported more
frequently in patients with advanced relapsed and refractory
multiple myeloma who received KYPROLIS monotherapy. Monitor renal
function with regular measurement of the serum creatinine and/or
estimated creatinine clearance. Reduce or withhold dose as
appropriate.
Tumor Lysis Syndrome
- Cases of Tumor Lysis Syndrome (TLS), including fatal outcomes,
have occurred. Patients with a high tumor burden should be
considered at greater risk for TLS. Adequate hydration is required
prior to each dose in Cycle 1, and in subsequent cycles as needed.
Consider uric acid lowering drugs in patients at risk for TLS.
Monitor for evidence of TLS during treatment and manage promptly,
and withhold until resolved.
Pulmonary Toxicity
- Acute Respiratory Distress Syndrome (ARDS), acute respiratory
failure, and acute diffuse infiltrative pulmonary disease such as
pneumonitis and interstitial lung disease have occurred. Some
events have been fatal. In the event of drug‐induced pulmonary
toxicity, discontinue KYPROLIS.
Pulmonary Hypertension
- Pulmonary arterial hypertension (PAH) was reported. Evaluate
with cardiac imaging and/or other tests as indicated. Withhold
KYPROLIS for PAH until resolved or returned to baseline and
consider whether to restart based on a benefit/risk
assessment.
Dyspnea
- Dyspnea was reported in patients treated with KYPROLIS.
Evaluate dyspnea to exclude cardiopulmonary conditions including
cardiac failure and pulmonary syndromes. Stop KYPROLIS for Grade 3
or 4 dyspnea until resolved or returned to baseline. Consider
whether to restart based on a benefit/risk assessment.
Hypertension
- Hypertension, including hypertensive crisis and hypertensive
emergency, has been observed, some fatal. Control hypertension
prior to starting KYPROLIS. Monitor blood pressure regularly in all
patients. If hypertension cannot be adequately controlled, withhold
KYPROLIS and evaluate. Consider whether to restart based on a
benefit/risk assessment.
Venous Thrombosis
- Venous thromboembolic events (including deep venous thrombosis
and pulmonary embolism) have been observed. Thromboprophylaxis is
recommended for patients being treated with the combination of
KYPROLIS with dexamethasone or with lenalidomide plus
dexamethasone. The thromboprophylaxis regimen should be based on an
assessment of the patient's underlying risks.
- Patients using hormonal contraception associated with a risk of
thrombosis should consider an alternative method of effective
contraception during treatment.
Infusion Reactions
- Infusion reactions, including life‐threatening reactions, have
occurred. Symptoms include fever, chills, arthralgia, myalgia,
facial flushing, facial edema, vomiting, weakness, shortness of
breath, hypotension, syncope, chest tightness, or angina. These
reactions can occur immediately following or up to 24 hours after
administration. Premedicate with dexamethasone to reduce the
incidence and severity of infusion reactions. Inform patients of
the risk and of symptoms and seek immediate medical attention if
they occur.
Hemorrhage
- Fatal or serious cases of hemorrhage have been reported.
Hemorrhagic events have included gastrointestinal, pulmonary, and
intracranial hemorrhage and epistaxis. Promptly evaluate signs and
symptoms of blood loss. Reduce or withhold dose as
appropriate.
Thrombocytopenia
- KYPROLIS causes thrombocytopenia with recovery to baseline
platelet count usually by the start of the next cycle. Monitor
platelet counts frequently during treatment. Reduce or withhold
dose as appropriate.
Hepatic Toxicity and Hepatic Failure
- Cases of hepatic failure, including fatal cases, have occurred.
KYPROLIS can cause increased serum transaminases. Monitor liver
enzymes regularly regardless of baseline values. Reduce or withhold
dose as appropriate.
Thrombotic Microangiopathy
- Cases of thrombotic microangiopathy, including thrombotic
thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS),
including fatal outcome have occurred. Monitor for signs and
symptoms of TTP/HUS. Discontinue if diagnosis is suspected. If the
diagnosis of TTP/HUS is excluded, KYPROLIS may be restarted. The
safety of reinitiating KYPROLIS is not known.
Posterior Reversible Encephalopathy Syndrome (PRES)
- Cases of PRES have occurred in patients receiving KYPROLIS. If
PRES is suspected, discontinue and evaluate with appropriate
imaging. The safety of reinitiating KYPROLIS is not known.
Increased Fatal and Serious Toxicities in Combination with
Melphalan and Prednisone in Newly Diagnosed
Transplant-ineligible Patients
- In a clinical trial of transplant-ineligible patients with
newly diagnosed multiple myeloma comparing KYPROLIS, melphalan, and
prednisone (KMP) vs bortezomib, melphalan, and prednisone (VMP), a
higher incidence of serious and fatal adverse events was observed
in patients in the KMP arm. KMP is not indicated for
transplant-ineligible patients with newly diagnosed multiple
myeloma.
Embryo-fetal Toxicity
- KYPROLIS can cause fetal harm when administered to a pregnant
woman.
- Females of reproductive potential should be advised to avoid
becoming pregnant while being treated with KYPROLIS and for 6
months following the final dose. Males of reproductive potential
should be advised to avoid fathering a child while being treated
with KYPROLIS and for 3 months following the final dose. If this
drug is used during pregnancy, or if pregnancy occurs while taking
this drug, the patient should be apprised of the potential hazard
to the fetus.
ADVERSE REACTIONS
- The most common adverse reactions in the combination therapy
trials: anemia, neutropenia, diarrhea, dyspnea, fatigue,
thrombocytopenia, pyrexia, insomnia, muscle spasm, cough, upper
respiratory tract infection, hypokalemia.
- The most common adverse reactions in monotherapy trials:
anemia, fatigue, thrombocytopenia, nausea, pyrexia, dyspnea,
diarrhea, headache, cough, edema peripheral
Please see full Prescribing Information
at www.kyprolis.com.
About Amgen Oncology
Amgen Oncology is searching for
and finding answers to incredibly complex questions that will
advance care and improve lives for cancer patients and their
families. Our research drives us to understand the disease in the
context of the patient's life – not just their cancer journey – so
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For the last four decades, we have been dedicated to discovering
the firsts that matter in oncology and to finding ways to reduce
the burden of cancer. Building on our heritage, Amgen continues to
advance the largest pipeline in the Company's history, moving with
great speed to advance those innovations for the patients who need
them.
At Amgen, we are driven by our commitment to transform the lives
of cancer patients and keep them at the center of everything we
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For more information, follow us on
www.twitter.com/amgenoncology.
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Amgen is committed to unlocking
the potential of biology for patients suffering from serious
illnesses by discovering, developing, manufacturing and delivering
innovative human therapeutics. This approach begins by using tools
like advanced human genetics to unravel the complexities of disease
and understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and
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For more information, visit www.amgen.com and follow
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CONTACT: Amgen, Thousand
Oaks
Trish Hawkins, 805-447-5631
(media)
Jessica Akopyan, 805-447-0974
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Arvind Sood, 805-447-1060
(investors)
References:
- Jakubowiak A. Management strategies for relapsed/refractory
multiple myeloma: current clinical perspectives. Semin
Hematol. 2012 Jul; 49 Suppl 1:S16-S32.
- GLOBOCAN 2018. Global Prevalence and Incidence. Available
at: http://globocan.iarc.fr/old/summary_table_pop_prev.asp?selection=224900&title=World&sex=0&window=1&sort=0&submit=%C2%A0Execute%C2%A0http://globocan.iarc.fr/old/summary_table_pop_prev.asp?selection=224900&title=World&sex=0&window=1&sort=0&submit=%C2%A0Execute%C2%A0.
Accessed on: July 18, 2019.
- American Cancer Society. About Multiple Myeloma. Available
at: https://www.cancer.org/content/dam/CRC/PDF/Public/8738.00.pdf.
Accessed on: July 18, 2019.
- Moreau P, Richardson PG, Cavo M, et al. Proteasome inhibitors
in multiple myeloma: 10 years later. Blood. 2012
Aug 2;120(5):947-59.
- Kortuem KM and Stewart AK. Carfilzomib. Blood. 2013
Feb 7;121(6):893-7.
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