– Results are from 1,500 patient trial
conducted by German Hodgkin Study Group to test ADCETRIS regimen
versus international standard eBEACOPP therapy
– ADCETRIS regimen showed less peripheral
neuropathy
Seagen Inc. (NASDAQ: SGEN) today announced that the clinical
research cooperative German Hodgkin Study Group (GHSG) presented
results showing that a phase 3 trial of ADCETRIS® in combination
with chemotherapy – a regimen called BrECADD (brentuximab vedotin
[ADCETRIS], etoposide, cyclophosphamide, doxorubicin [Adriamycin],
dacarbazine, and dexamethasone) – met its co-primary endpoints of
non-inferior efficacy and superior tolerability versus a highly
efficacious yet chemotherapy-intense treatment regimen of escalated
BEACOPP (bleomycin, etoposide, doxorubicin (Adriamycin),
cyclophosphamide, vincristine, procarbazine, and prednisone), which
is an international standard of care in the frontline advanced
classical Hodgkin lymphoma (cHL) setting and commonly used in
Europe. Both study arms used PET scans to guide treatment
decisions. The data results of the HD21 study were presented in a
late-breaking session at the 17th International Conference on
Malignant Lymphoma (ICML) in Lugano, Switzerland on June 17.
An interim analysis at 40 months showed an unprecedented 94.9%
3-year progression-free survival (PFS) (99% CI: 92.8, 97.1) for
patients treated with the ADCETRIS combination of BrECADD versus
92.3% for eBEACOPP (99% CI: 89.7, 94.9). 12-month post-treatment
safety data were consistent with previously presented HD21 data
results at the American Society of Hematology 2022 Annual
Meeting.
ADCETRIS + AVD chemotherapy (Adriamycin, vinblastine,
dacarbazine) is a U.S. standard of care in advanced-stage cHL and
is the only targeted therapy inclusive regimen that has a proven
statistically significant overall survival benefit at 6-years of
follow-up compared to ABVD, reducing risk of death by 41% for these
patients.i,ii ADCETRIS is approved for seven indications in the
U.S. and six indications in Europe, where Takeda has
commercialization rights.
“Our mission in Hodgkin lymphoma is to cure patients with a
first-line treatment that reduces the risk of cancer returning as
much as possible so patients can go on with their lives,” said
Professor Dr. med. Peter Borchmann, Assistant Medical Director,
Department of Hematology and Oncology at the University Hospital of
Cologne, Germany and Head of the Lymphoma Program, Head of the
German Hodgkin Study Group and Trial Chairman of the HD21 study.
“The mature results of this study demonstrate 3-year efficacy never
previously observed in a phase 3 trial in advanced cHL and suggest
that the BrECADD regimen may be the most effective therapy regimen
currently available in advanced cHL.”
“We are enthusiastic about these strong and durable efficacy
outcomes and tolerability findings of an ADCETRIS based
chemotherapy regimen compared to an international standard
chemotherapy. We are evaluating these results to determine next
steps,” said Roger Dansey, President of Research and Development
and Chief Medical Officer at Seagen.
Results from the GHSG’s HD21 Trial
Among 1,482 patients at median follow up of 40 months, an
intent-to-treat analysis showed:
- 3-year PFS was 94.9% for BrECADD vs. 92.3% for eBEACOPP
(HR=0.63 [99% CI: 0.37, 1.07])
- 1-year PFS was 97.5% for BrECADD (99% CI: 96, 99)
- 3-year overall survival was 98.5% in both treatment arms
12-month post-treatment safety information was available for 95
percent of patients (n=1,395), which showed the rate of grade ≥2
peripheral neuropathy was lower with BrECADD (1.9%) vs. eBEACOPP
(2.7%) with most patients having no or low (grade 1) peripheral
neuropathy (98.1% for BrECADD vs. 97.3% for eBEACOPP).
Preservation of fertility potential was indicated by measurement
of follicle-stimulating hormone (FSH) and was available for 597
patients. Preservation of fertility potential was numerically
favorable for the BrECADD arm vs. eBEACOPP. Mean FSH levels were
29.4 and 31.8 after 4 and 6 cycles, respectively for eBEACOPP, and
18.3 and 20.5 after 4 and 6 cycles, respectively, for BrECADD.
Persistently elevated FSH is associated with impaired gonadal
function. Additional analysis is required to understand the
significance of these findings.
Please see Important Safety Information, including a
BOXED WARNING for progressive multifocal
leukoencephalopathy (PML), for ADCETRIS below.
About the HD21 Study
The GHSG’s phase 3 HD21 trial in advanced cHL enrolled 1,500
patients from 9 countries between July 2016 and August 2020. The
median age was 34 years old (range 18-61), and 47 percent were
considered high-risk with an international prognostic index ≥3. 59%
of patients received four cycles of therapy and 41% received six
cycles of therapy. Patients were randomized in a 1:1 ratio to
PET2-guided 4-6 cycles of either BrECADD or eBEACOPP. PET2 and PFS
events were assessed by blinded panel review. Non-inferiority of
the primary efficacy endpoint PFS was defined as absolute
difference <6% at five years corresponding to an HR of BrECADD
vs eBEACOPP <1.69. The study was funded by Takeda.
About Hodgkin Lymphoma
Lymphoma is a general term for a group of cancers that originate
in the lymphatic system affecting a type of white blood cell called
lymphocytes. There are two major categories of lymphoma: Hodgkin
lymphoma and non-Hodgkin lymphoma. Hodgkin lymphoma is
distinguished by the presence of Reed-Sternberg cells that usually
have a protein called CD30 on their surface. Approximately 8,830
cases of classical Hodgkin lymphoma will be diagnosed in the United
States during 2023 and 900 people will die from the disease.iii
According to the International Agency for Research on Cancer in
2020, over 83,000 people worldwide were diagnosed with Hodgkin
lymphoma and approximately 23,000 people died from this
cancer.iv
About The German Hodgkin Study Group
For over 30 years, the German Hodgkin Study Group (GHSG) has
been committed to optimizing diagnostics, therapy and follow-up
care in Hodgkin lymphoma. The GHSG’s Trial Coordination Center
belongs to the Department of Internal Medicine at the University of
Cologne. It recruits patients from across Europe, and over 15,000
patients have participated in its clinical trials. With the results
of its large-scale controlled, prospective and randomized trials
for all stages of Hodgkin lymphoma, the GHSG has contributed
decisively to the great progress in Hodgkin lymphoma therapy over
the years. The GHSG’s latest trials aim to reduce adverse effects
of therapy while maintaining cure rates.
About ADCETRIS
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 Seagen'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 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)
ADCETRIS has marketing authorization in more than 70 countries
for relapsed or refractory Hodgkin lymphoma and systemic anaplastic
large cell lymphoma. ADCETRIS received conditional marketing
authorization from the European Commission in October 2012. Its
approved indications in Europe are for:
- Adult patients with previously untreated CD30-positive Stage IV
Hodgkin lymphoma in combination with AVD
- Adult patients with CD30-positive Hodgkin lymphoma at increased
risk of relapse or progression following ASCT.
- Adult patients with relapsed or refractory CD30-positive
Hodgkin lymphoma following ASCT or following at least two prior
therapies when ASCT or multi-agent chemotherapy is not a treatment
option.
- Adult patients with relapsed or refractory sALCL
- Adult patients with previously untreated sALCL in combination
with CHP
- Adult patients with CD30-positive cutaneous T-cell lymphoma
(CTCL) after at least one prior systemic therapy
Seagen and Takeda jointly develop ADCETRIS. Under the terms of
the collaboration agreement, Seagen has U.S. and Canadian
commercialization rights, and Takeda has rights to commercialize
ADCETRIS in the rest of the world. Seagen 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 Seagen
Founded 25 years ago, Seagen Inc. is a global biotechnology
company that discovers, develops, manufactures and commercializes
targeted cancer therapeutics, with antibody-drug conjugates (ADCs)
at our core. Our colleagues work together with urgency to improve
and extend the lives of people living with cancer. An ADC
technology trailblazer, approximately one-third of FDA-approved and
marketed ADCs use Seagen technology. Seagen is headquartered in
Bothell, Washington and has locations in California, Canada,
Switzerland and across Europe. For additional information, visit
seagen.com and follow us on Twitter and LinkedIn.
Forward-Looking Statements
Certain statements made in this press release are forward
looking, such as those, among others, relating to the therapeutic
potential of ADCETRIS, its safety, efficacy and therapeutic uses.
Actual results or developments may differ materially from those
projected or implied in these forward-looking statements. Factors
that may cause such a difference include without limitation the
risk of delays, setbacks or failures in product development
activities, even after encouraging results in earlier-stage trials,
for a variety of reasons, including without limitation the
difficulty and uncertainty of pharmaceutical product development,
the possibility that clinical results may not support continued
development or regulatory approvals, the risk of adverse events or
safety signals, and the possibility of adverse regulatory actions.
More information about the risks and uncertainties faced by Seagen
is contained under the caption “Risk Factors” included in Seagen’s
Quarterly Report on Form 10-Q for the quarter ended March 31, 2023,
and Seagen’s subsequent reports, filed with the Securities and
Exchange Commission. Seagen disclaims any intention or obligation
to update or revise any forward-looking statements, whether as a
result of new information, future events or otherwise except as
required by applicable law.
i
https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1439
ii https://www.nejm.org/doi/full/10.1056/NEJMoa2206125 iii
https://www.cancer.org/cancer/hodgkin-lymphoma/about/key-statistics.html
iv
https://gco.iarc.fr/today/data/factsheets/cancers/33-Hodgkin-lymphoma-fact-sheet.pdf
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version on businesswire.com: https://www.businesswire.com/news/home/20230620669848/en/
For Media David Caouette (310) 430-3476 dcaouette@seagen.com
For Investors Douglas Maffei, Ph.D. (425) 527-4160 dmaffei@seagen.com
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