– Updated phase 2 data results presented for
ADCETRIS in combination with immune therapy nivolumab and
doxorubicin and dacarbazine chemotherapy –
– Regimen well-tolerated with fewer than half
of patients developing primarily low-grade peripheral neuropathy
and no cases of febrile neutropenia –
Seagen Inc. (NASDAQ: SGEN) today announced updated efficacy and
safety results from Part C of a phase 2 single-arm trial
(SGN35-027) evaluating the antibody-drug conjugate ADCETRIS®
(brentuximab vedotin) in combination with the PD-1 inhibitor
nivolumab and standard chemotherapy agents doxorubicin and
dacarbazine (AN+AD) for the frontline treatment of patients with
early-stage classical Hodgkin lymphoma (cHL). Data results will be
presented at the 17th International Conference on Malignant
Lymphoma (ICML) in Lugano, Switzerland June 13-17.
Also, to be presented in a late-breaking session, are three-year
results from a 1,500-patient phase 3 trial from the German Hodgkin
Study Group (HD21) evaluating non-inferiority efficacy and
potential for reduced toxicity of an ADCETRIS regimen (BrECADD)
compared to the highly efficacious yet chemotherapy intensive
escalated BEACOPP regimen, commonly used outside of the U.S. The
study will be presented on June 17, 2023.
ADCETRIS + AVD chemotherapy (Adriamycin, vinblastine,
dacarbazine) is a U.S. standard of care in advanced-stage cHL based
on national treatment guidelines and is the only targeted therapy
inclusive regimen that has a proven statistically significant
overall survival benefit at 6-years of follow-up, reducing risk of
death by 41% for these patients.i,ii ADCETRIS is approved for seven
indications in the U.S. and five indications in Europe, where
Takeda has commercialization rights.
“With teens and young adults primarily impacted by Hodgkin
lymphoma, our goal is to develop curative treatments that improve
survival while also reducing toxicity,” said Jeremy Abramson, MD,
Director, Jon and Jo Ann Hagler Center for Lymphoma at
Massachusetts General Hospital and principal investigator of the
trial. “The targeted agents of brentuximab vedotin and nivolumab
have distinct mechanisms of action and demonstrated promising
activity and safety in this early study; the omission of bleomycin
and vinblastine chemotherapy likely contributed to the absence of
certain adverse events.”
“We are encouraged by the promising clinical outcomes of an
ADCETRIS plus nivolumab combination with reduced chemotherapy as we
seek to maximize efficacy and improve tolerability in both early-
and late-stage classical Hodgkin lymphoma,” said Roger Dansey,
President of Research and Development and Chief Medical Officer at
Seagen.
New Results Presented from SGN35-027
Of 154 patients with early-stage disease in Part C of the study,
150 were included at the time of efficacy assessment, showing:
- A 98% ORR (95% CI: 94.3, 99.6) and a 93% CR rate (95% CI: 87.3,
96.3) at end of treatment (EOT).
- Follow-up is ongoing and progression-free survival (PFS)
results are not yet available.
- The most frequently reported treatment-related
treatment-emergent adverse events (TRAEs) of any grade occurring in
more than 30 percent of patients were nausea (65%), peripheral
sensory neuropathy (47%) and fatigue (44%).
- Peripheral sensory neuropathy was primarily low grade (3% Grade
≥3).
- There were no cases of febrile neutropenia.
- Immune-mediated AEs observed to date are consistent with the
individual safety profile of nivolumab.
- There were no grade 5 adverse events.
Updated data results from Part B of the study in patients with
advanced-stage disease (n=57) were presented at the European
Hematology Association 2023 Congress in Frankfurt, Germany June
8-11, which showed an estimated 95% 12-month PFS rate and 93%
18-month PFS rate, an ORR of 95% and CR rate of 89% at EOT. The
most frequently reported TRAEs of any grade occurring in more than
30 percent of patients were nausea (65%), fatigue (49%), peripheral
sensory neuropathy (44%) and alopecia (35%).
Please see Important Safety Information, including a
BOXED WARNING for progressive multifocal
leukoencephalopathy (PML), for ADCETRIS below.
About the SGN35-027 Clinical Study
SGN35-027 is an ongoing open-label, multiple part, multicenter,
phase 2 clinical trial evaluating two different brentuximab vedotin
treatment combinations in patients with advanced and early-stage
cHL. The trial includes three parts (Parts A, B, and C). Part A is
evaluating the combination of brentuximab vedotin and doxorubicin,
vinblastine, and dacarbazine (A+AVD) with primary
granulocyte-colony stimulating factor (G-CSF) prophylaxis, while
Parts B and C are evaluating brentuximab vedotin in combination
with nivolumab, doxorubicin, and dacarbazine (AN+AD) as a
first-line treatment in advanced and early-stage disease,
respectively. Part B is evaluating the combination in patients with
stage II bulky (mediastinal mass ≥10
cm), stage III or IV cHL. Part C is evaluating the combination in
patients with stage I or II cHL without bulky mediastinal disease
(<10 cm). The primary endpoint for Part A is the proportion of
patients with treatment-emergent febrile neutropenia. The primary
endpoint for Parts B and C is the proportion of participants with
complete response at end of treatment according to the Lymphoma
Response to Immunomodulatory Therapy Criteria (LYRIC). Incidence of
adverse events is a secondary endpoint for Parts B and C.
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 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 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 avoid
pregnancy during ADCETRIS treatment and for 6 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.
Females and Males of Reproductive Potential: Advise
females to report pregnancy immediately and advise males with
female sexual partners of reproductive potential to use effective
contraception during ADCETRIS treatment and for 6 months after the
last dose of ADCETRIS.
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
View source
version on businesswire.com: https://www.businesswire.com/news/home/20230613380261/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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