- Detailed data from Phase 3 ECHELON-3 study demonstrate
investigational ADCETRIS regimen reduced risk of death by 37
percent compared to chemotherapy alone, resulting in median overall
survival of 13.8 months versus 8.5 months
- Third Phase 3 trial in third type of lymphoma to show
improvement in overall survival with an ADCETRIS-containing
regimen
Pfizer Inc. (NYSE: PFE) today announced detailed overall
survival (OS) results from the Phase 3 ECHELON-3 study of ADCETRIS®
(brentuximab vedotin) in combination with lenalidomide and
rituximab for the treatment of patients with relapsed/refractory
diffuse large B-cell lymphoma (DLBCL). The study showed that the
ADCETRIS combination reduced patients’ risk of death by 37%
compared to placebo in combination with lenalidomide and rituximab
(HR 0.63 [95% CI: 0.445-0.891] p=0.0085). The overall survival
benefit was consistent across levels of CD30 expression.
The ECHELON-3 results will be presented as a late-breaker
(LBA7005) in an oral session at the 2024 American Society of
Clinical Oncology (ASCO) Annual Meeting along with four-year
results from the Phase 3 HD21 trial in advanced classical Hodgkin
lymphoma (cHL) (LBA7000).
“ECHELON-3 is one of the first randomized, placebo-controlled
Phase 3 studies to demonstrate an overall survival benefit in
patients with relapsed/refractory DLBCL after two or more prior
lines of systemic therapy,” said principal investigator Dr. Jeung-A
Kim, College of Medicine, The Catholic University of Korea. “The
clinically meaningful improvement in survival demonstrates the
potential benefit of this ADCETRIS regimen in relapsed/refractory
DLBCL, particularly for patients whose disease has progressed after
CAR-T therapy or bispecific antibody treatment or individuals who
are not able to receive these treatments.”
ADCETRIS is approved in the U.S. as monotherapy or in
combination with chemotherapy for seven lymphomas including certain
types of cHL, anaplastic large cell lymphoma and peripheral T-cell
lymphoma. Seven-year survival data for an ADCETRIS regimen for
patients with advanced stage cHL will be shared in a poster
presentation (7053) at the ASCO Meeting on June 3.
“Three Phase 3 trials in three different types of lymphoma have
now demonstrated that an ADCETRIS-containing regimen improved
overall survival,” said Roger Dansey, M.D., Chief Development
Officer, Oncology, Pfizer. “ADCETRIS is a standard of care medicine
in its approved indications today, and these impressive results
from an interim analysis highlight its potential to benefit people
with relapsed/refractory DLBCL regardless of CD30 expression.”
DLBCL is the most common lymphoma and is aggressive and
difficult to treat, with up to 40 percent of patients experiencing
disease progression after initial therapy.1,2
Among 230 randomized patients in the trial, the interim analysis
showed that median OS in patients randomized to receive ADCETRIS,
lenalidomide and rituximab was 13.8 months (95% CI: 10.3-18.8)
compared to 8.5 months (95% CI: 5.4-11.7) in patients randomized to
lenalidomide and rituximab plus placebo.
Median progression-free survival (PFS) was 4.2 months (95% CI:
2.9-7.1) in the ADCETRIS arm versus 2.6 months (95% CI: 1.4-3.1) in
the lenalidomide and rituximab plus placebo arm (HR 0.527 [95% CI:
0.380-0.729] p<0.0001). The overall response rate for patients
treated with the ADCETRIS regimen was 64.3% (95% CI: 54.7-73.1)
versus 41.5% (95% CI: 32.5-51.0) in the lenalidomide and rituximab
plus placebo arm. The complete response rate was 40.2% in
ADCETRIS-treated patients (95% CI: 31.0%, 49.9%) compared to 18.6%
(95% CI:12.1%, 26.9%) in the lenalidomide and rituximab plus
placebo arm.
The most frequently reported treatment-emergent adverse events
(TEAEs) Grade 3 or higher for the ADCETRIS versus placebo arms
were: neutropenia (43% vs 28%), thrombocytopenia (25% vs 19%) and
anemia (22% vs 21%). Peripheral sensory neuropathy was infrequent
and low grade for each arm with Grade 3 events of 4% vs 0%.
About ECHELON-3 ECHELON-3 is an ongoing,
randomized, double-blind, multicenter Phase 3 study evaluating
ADCETRIS plus lenalidomide and rituximab versus lenalidomide and
rituximab plus placebo in adult patients with relapsed/refractory
DLBCL, regardless of CD30 expression, who have received two or more
prior lines of therapy and are ineligible for stem cell transplant
or CAR-T therapy. In this global study, 230 patients were
randomized across North America, Europe and Asia-Pacific. The
primary endpoint is OS in the intent to treat population, with key
secondary endpoints of PFS and ORR as assessed by investigator.
Other secondary endpoints include complete response rate, duration
of response, safety and tolerability.
About Diffuse Large B-cell Lymphoma DLBCL is
the most frequent type of lymphoma and is aggressive and difficult
to treat.1,2 More than 25,000 cases of DLBCL are diagnosed each
year in the United States, accounting for more than 25 percent of
all lymphoma cases.2 DLBCL can develop spontaneously or as a result
of diseases such as chronic lymphocytic lymphoma/small lymphocytic
lymphoma, follicular lymphoma, or marginal zone lymphoma.1 Up to 40
percent of patients relapse or have refractory disease after
frontline treatment.2
About ADCETRIS More than 55,000 patients have been
treated with ADCETRIS in the U.S. since its first U.S. approval in
2011, and more than 140,000 patients have been treated with
ADCETRIS globally.
ADCETRIS is an antibody-drug conjugate (ADC) comprised of a
CD30-directed monoclonal antibody attached by a protease-cleavable
linker to a microtubule disrupting agent, monomethyl auristatin E
(MMAE), utilizing Pfizer's proprietary technology. The ADC employs
a linker system that is designed to be stable in the bloodstream
but to release MMAE upon internalization into CD30-positive tumor
cells.
ADCETRIS is approved in seven indications in the U.S.:
- Adult patients with previously untreated Stage III/IV classical
Hodgkin lymphoma (cHL) in combination with doxorubicin,
vinblastine, and dacarbazine (2018)
- Pediatric patients 2 years and older with previously untreated
high risk cHL in combination with doxorubicin, vincristine,
etoposide, prednisone and cyclophosphamide (2022)
- Adult patients with cHL at high risk of relapse or progression
as post-autologous hematopoietic stem cell transplantation
(auto-HSCT) consolidation (2015)
- Adult patients with cHL after failure of auto-HSCT or after
failure of at least two prior multi-agent chemotherapy regimens in
patients who are not auto-HSCT candidates (2011)
- Adult patients with previously untreated systemic anaplastic
large cell lymphoma (sALCL) or other CD30-expressing peripheral
T-cell lymphomas (PTCL), including angioimmunoblastic T-cell
lymphoma and PTCL not otherwise specified, in combination with
cyclophosphamide, doxorubicin, and prednisone (2018)
- Adult patients with sALCL after failure of at least one prior
multi-agent chemotherapy regimen. (2011)
- Adult patients with primary cutaneous anaplastic large cell
lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) after
prior systemic therapy (2017)
Pfizer and Takeda jointly develop ADCETRIS. Under the terms of
the collaboration agreement, Pfizer has U.S. and Canadian
commercialization rights, and Takeda has rights to commercialize
ADCETRIS in the rest of the world. Pfizer and Takeda are funding
joint development costs for ADCETRIS on a 50:50 basis, except in
Japan where Takeda is solely responsible for development costs.
ADCETRIS® (brentuximab vedotin) for injection U.S. Important
Safety Information
BOXED WARNING
PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): JC virus
infection resulting in PML, and death can occur in ADCETRIS-treated
patients.
CONTRAINDICATION Contraindicated with concomitant
bleomycin due to pulmonary toxicity (e.g., interstitial
infiltration and/or inflammation).
WARNINGS AND PRECAUTIONS
Peripheral neuropathy (PN): ADCETRIS causes PN that is
predominantly sensory. Cases of motor PN have also been reported.
ADCETRIS-induced PN is cumulative. Monitor for symptoms such as
hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning
sensation, neuropathic pain, or weakness. Patients experiencing new
or worsening PN may require a delay, change in dose, or
discontinuation of ADCETRIS.
Anaphylaxis and infusion reactions: Infusion-related
reactions (IRR), including anaphylaxis, have occurred with
ADCETRIS. Monitor patients during infusion. If an IRR occurs,
interrupt the infusion and institute appropriate medical
management. If anaphylaxis occurs, immediately and permanently
discontinue the infusion and administer appropriate medical
therapy. Premedicate patients with a prior IRR before subsequent
infusions. Premedication may include acetaminophen, an
antihistamine, and a corticosteroid.
Hematologic toxicities: Fatal and serious cases of
febrile neutropenia have been reported with ADCETRIS. Prolonged (≥1
week) severe neutropenia and Grade 3 or 4 thrombocytopenia or
anemia can occur with ADCETRIS.
Administer G-CSF primary prophylaxis beginning with Cycle 1 for
adult patients who receive ADCETRIS in combination with
chemotherapy for previously untreated Stage III/IV cHL or
previously untreated PTCL, and pediatric patients who receive
ADCETRIS in combination with chemotherapy for previously untreated
high risk cHL.
Monitor complete blood counts prior to each ADCETRIS dose.
Monitor more frequently for patients with Grade 3 or 4 neutropenia.
Monitor patients for fever. If Grade 3 or 4 neutropenia develops,
consider dose delays, reductions, discontinuation, or G-CSF
prophylaxis with subsequent doses.
Serious infections and opportunistic infections:
Infections such as pneumonia, bacteremia, and sepsis or septic
shock (including fatal outcomes) have been reported in
ADCETRIS-treated patients. Closely monitor patients during
treatment for infections.
Tumor lysis syndrome: Patients with rapidly proliferating
tumor and high tumor burden may be at increased risk. Monitor
closely and take appropriate measures.
Increased toxicity in the presence of severe renal
impairment: The frequency of ≥Grade 3 adverse reactions and
deaths was greater in patients with severe renal impairment. Avoid
use in patients with severe renal impairment.
Increased toxicity in the presence of moderate or severe
hepatic impairment: The frequency of ≥Grade 3 adverse reactions
and deaths was greater in patients with moderate or severe hepatic
impairment. Avoid use in patients with moderate or severe hepatic
impairment.
Hepatotoxicity: Fatal and serious cases have occurred in
ADCETRIS-treated patients. Cases were consistent with
hepatocellular injury, including elevations of transaminases and/or
bilirubin, and occurred after the first ADCETRIS dose or
rechallenge. Preexisting liver disease, elevated baseline liver
enzymes, and concomitant medications may increase the risk. Monitor
liver enzymes and bilirubin. Patients with new, worsening, or
recurrent hepatotoxicity may require a delay, change in dose, or
discontinuation of ADCETRIS.
PML: Fatal cases of JC virus infection resulting in PML
have been reported in ADCETRIS-treated patients. First onset of
symptoms occurred at various times from initiation of ADCETRIS,
with some cases occurring within 3 months of initial exposure. In
addition to ADCETRIS therapy, other possible contributory factors
include prior therapies and underlying disease that may cause
immunosuppression. Consider PML diagnosis in patients with
new-onset signs and symptoms of central nervous system
abnormalities. Hold ADCETRIS if PML is suspected and discontinue
ADCETRIS if PML is confirmed.
Pulmonary toxicity: Fatal and serious events of
noninfectious pulmonary toxicity, including pneumonitis,
interstitial lung disease, and acute respiratory distress syndrome,
have been reported. Monitor patients for signs and symptoms,
including cough and dyspnea. In the event of new or worsening
pulmonary symptoms, hold ADCETRIS dosing during evaluation and
until symptomatic improvement.
Serious dermatologic reactions: Fatal and serious cases
of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis
(TEN) have been reported with ADCETRIS. If SJS or TEN occurs,
discontinue ADCETRIS and administer appropriate medical
therapy.
Gastrointestinal (GI) complications: Fatal and serious
cases of acute pancreatitis have been reported. Other fatal and
serious GI complications include perforation, hemorrhage, erosion,
ulcer, intestinal obstruction, enterocolitis, neutropenic colitis,
and ileus. Lymphoma with pre-existing GI involvement may increase
the risk of perforation. In the event of new or worsening GI
symptoms, including severe abdominal pain, perform a prompt
diagnostic evaluation and treat appropriately.
Hyperglycemia: Serious cases, such as new-onset
hyperglycemia, exacerbation of pre-existing diabetes mellitus, and
ketoacidosis (including fatal outcomes) have been reported with
ADCETRIS. Hyperglycemia occurred more frequently in patients with
high body mass index or diabetes. Monitor serum glucose and if
hyperglycemia develops, administer anti-hyperglycemic medications
as clinically indicated.
Embryo-fetal toxicity: Based on the mechanism of action
and animal studies, ADCETRIS can cause fetal harm. Advise females
of reproductive potential of this potential risk, and to use
effective contraception during ADCETRIS treatment and for 2 months
after the last dose of ADCETRIS. Advise male patients with female
partners of reproductive potential to use effective contraception
during ADCETRIS treatment and for 4 months after the last dose of
ADCETRIS.
ADVERSE REACTIONS The most common adverse reactions
(≥20% in any study) are peripheral neuropathy, fatigue, nausea,
diarrhea, neutropenia, upper respiratory tract infection, pyrexia,
constipation, vomiting, alopecia, decreased weight, abdominal pain,
anemia, stomatitis, lymphopenia, mucositis, thrombocytopenia, and
febrile neutropenia.
DRUG INTERACTIONS Concomitant use of strong CYP3A4
inhibitors has the potential to affect the exposure to monomethyl
auristatin E (MMAE). Closely monitor adverse reactions.
USE IN SPECIAL POPULATIONS
Lactation: Breastfeeding is not recommended during
ADCETRIS treatment.
Please see the full Prescribing Information, including BOXED
WARNING, for ADCETRIS here.
About Pfizer Oncology At Pfizer Oncology, we are at
the forefront of a new era in cancer care. Our industry-leading
portfolio and extensive pipeline includes three core mechanisms of
action to attack cancer from multiple angles, including small
molecules, antibody-drug conjugates (ADCs), and bispecific
antibodies, including other immune-oncology biologics. We are
focused on delivering transformative therapies in some of the
world’s most common cancers, including breast cancer, genitourinary
cancer, hematology-oncology, and thoracic cancers, which includes
lung cancer. Driven by science, we are committed to accelerating
breakthroughs to help people with cancer live better and longer
lives.
About Pfizer: Breakthroughs That Change Patients’
Lives 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, including innovative medicines
and vaccines. 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 health care around the world.
For 175 years, we have worked to make a difference for all who rely
on us. We routinely post information that may be important to
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more, please visit us on www.pfizer.com and follow us on X at
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at Facebook.com/Pfizer.
Disclosure Notice The information contained in this
release is as of June 1, 2024. 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 Pfizer
Oncology and ADCETRIS (brentuximab vedotin), including its
potential benefits, its potential for relapsed/refractory diffuse
large B-cell lymphoma (DLBCL) and the ongoing investigational trial
for ADCETRIS in combination with lenalidomide and rituximab, 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 ADCETRIS;
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; 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 drug applications may be filed in particular
jurisdictions for ADCETRIS with lenalidomide and rituximab or as a
single agent for any potential indication; whether and when any
applications that may be pending or filed for ADCETRIS may be
approved by regulatory authorities, 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 ADCETRIS with
lenalidomide and rituximab or as a single agent 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 ADCETRIS with lenalidomide and rituximab or as a single agent;
uncertainties regarding the impact of COVID-19 on Pfizer’s
business, operations and financial results; 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, 2023 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.
1 National Library of Medicine. Diffuse Large B-Cell Lymphoma.
https://www.ncbi.nlm.nih.gov/books/NBK557796/. Updated April 24,
2023. 2 Leukemia & Lymphoma Society. Diffuse Large B-Cell
Lymphoma (DLBCL).
https://www.lls.org/research/diffuse-large-b-cell-lymphoma-dlbcl
Category: Medicines, Research
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Pfizer (NYSE:PFE)
過去 株価チャート
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Pfizer (NYSE:PFE)
過去 株価チャート
から 6 2023 まで 6 2024
