- Additional Analysis in Phase 2 Trial of
ADCETRIS plus OPDIVO in Patients with Frontline Hodgkin Lymphoma
Aged 60 Years and Older -
- Two-Year Follow-up Results from Phase 1/2
Trial in Relapsed Hodgkin Lymphoma -
Seattle Genetics, Inc. (Nasdaq:SGEN) today announced updated and
long-term follow-up analyses from two clinical trials evaluating
ADCETRIS (brentuximab vedotin) and OPDIVO® (nivolumab) in frontline
Hodgkin lymphoma (HL) patients aged 60 years and older and in
relapsed or refractory classical HL. ADCETRIS is an antibody-drug
conjugate (ADC) directed to CD30, a defining marker of classical
HL. ADCETRIS and OPDIVO are not approved in combination for the
treatment of HL. Results were presented today at the 61st American
Society of Hematology (ASH) Annual Meeting and Exposition taking
place December 7-10 in Orlando, Fla.
“We continue to evaluate ADCETRIS in combination with novel
therapies, such as checkpoint inhibitors, with the goal of
identifying new options for CD30-expressing lymphomas where there
is high unmet need,” said Roger Dansey, M.D., Chief Medical Officer
at Seattle Genetics. “These data presentations at ASH reinforce our
strong commitment to the ADCETRIS clinical development program,
potentially moving into new patient populations and novel
combination treatment strategies.”
Phase 2 Study of Frontline Brentuximab Vedotin Plus Nivolumab
in Patients with Hodgkin Lymphoma Aged ≥ 60 Years (Abstract #237,
oral presentation at 2:30 p.m. ET on Saturday, December 7,
2019) Data were presented from an updated analysis from the
phase 2 clinical trial evaluating ADCETRIS in combination with
OPDIVO as frontline therapy for HL patients aged 60 years and
older. Data were reported from 21 patients, and the median age was
72 years. The majority of patients (76 percent) had stage III/IV
disease at the time of diagnosis. These results will be highlighted
in an oral presentation by Christopher A. Yasenchak, M.D.,
Willamette Valley Cancer Institute and Research Center/US Oncology
Research, Ore., and include:
- Of 19 response-evaluable patients, 18 patients (95 percent) had
an objective response, including 13 patients (68 percent) with a
complete response and five patients (26 percent) with a partial
response. All response-evaluable patients experienced tumor
reduction (complete response + partial response + stable disease)
following treatment with ADCETRIS in combination with OPDIVO.
Median duration of response was not yet reached and the maximum
duration of response was 22 months and ongoing (95% CI: 7.06,
-).
- The most common treatment-related adverse events of any grade
occurring in at least 20 percent of patients were fatigue,
diarrhea, pyrexia, infusion related reaction, peripheral motor
neuropathy, peripheral sensory neuropathy and increase in lipase.
One treatment-related serious adverse event was pyrexia.
Fifty-seven percent of patients (12/21) had at least one
treatment-related adverse event greater than or equal to Grade 3,
most commonly increase in lipase (24 percent, 5/21), peripheral
motor neuropathy and peripheral sensory neuropathy (each 14
percent, 3/21), and fatigue and hyponatremia (each 10 percent,
2/21).
Two-Year Follow-up Results from the Phase 1-2 Study of
Brentuximab Vedotin in Combination with Nivolumab in Patients with
Relapsed or Refractory Classical Hodgkin Lymphoma (Abstract #238,
oral presentation at 2:45 p.m. ET on Saturday, December 7,
2019) Data were reported from 93 patients with relapsed or
refractory classical HL after failure of frontline therapy who
received the combination regimen of ADCETRIS plus OPDIVO. After
completion of the fourth cycle of treatment, patients were eligible
to undergo an autologous stem cell transplant (ASCT). The median
age of patients was 34 years. These results will be highlighted in
an oral presentation by Alison J. Moskowitz, M.D., Memorial Sloan
Kettering Cancer Center, NY, and include:
- Of the 91 treated patients, 85 percent (77/91) had an objective
response, including 67 percent (61/91) with a complete response, 16
patients with a partial response and six patients had stable
disease.
- Of the 91 treated patients, 67 patients received an ASCT per
trial protocol with no additional salvage therapy.
- For all treated patients, the two-year progression-free
survival (PFS) was 79 percent (95% CI: 68%, 87%). For the 67
patients who received an ASCT per trial protocol, the two-year PFS
was 92 percent (95% CI: 80%, 97%). Median follow-up for all treated
patients was 24.2 months (range 1.8-41.7) and the median PFS was
not reached. Estimated overall survival at two years was 94 percent
(95% CI: 85%, 97%) and median overall survival was not yet
reached.
- Peripheral immune signatures were consistent with an activated
T-cell response.
- Prior to ASCT, the most common adverse events of any grade
occurring in more than 20 percent of patients were nausea, infusion
related reaction, fatigue, diarrhea, pruritus, headache, vomiting
and pyrexia. Other adverse events included peripheral neuropathy in
16 patients (18 percent) and neutropenia in six patients (7
percent). Two patients (2 percent) discontinued treatment due to
adverse events, Grade 3 peripheral neuropathy and increased
gamma-glutamyltransferase. Serious adverse events occurred in 14
patients (15 percent), including pneumonia, pneumonitis and pyrexia
(two patients each); and Grade 3 Guillain-Barre syndrome (one
patient).
About Classical Hodgkin Lymphoma Lymphoma is a general
term for a group of cancers that originate in the lymphatic system.
There are two major categories of lymphoma: Hodgkin lymphoma and
non-Hodgkin lymphoma. Classical Hodgkin lymphoma is distinguished
from other types of lymphoma by the presence of one characteristic
type of cell, known as the Reed-Sternberg cell. The Reed-Sternberg
cell expresses CD30.
According to the American Cancer Society, approximately 8,110
cases of Hodgkin lymphoma will be diagnosed in the United States
during 2019 and 1,000 will die from the disease. Approximately half
of all newly diagnosed Hodgkin lymphoma patients have Stage III/IV
disease. According to the Lymphoma Coalition, over 62,000 people
worldwide are diagnosed with Hodgkin lymphoma each year and
approximately 25,000 people die each year from this cancer.
About ADCETRIS ADCETRIS is being evaluated broadly in
more than 70 clinical trials in CD30-expressing lymphomas. These
include three completed phase 3 trials: ECHELON-2 trial in
frontline peripheral T-cell lymphomas, ECHELON-1 in previously
untreated Hodgkin lymphoma, and ALCANZA in cutaneous T-cell
lymphoma.
ADCETRIS is an ADC comprising an anti-CD30 monoclonal antibody
attached by a protease-cleavable linker to a microtubule disrupting
agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’
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-expressing tumor cells.
ADCETRIS injection for intravenous infusion has received FDA
approval for six indications in adult patients with: (1) 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, (2) previously untreated Stage III or IV classical
Hodgkin lymphoma (cHL), in combination with doxorubicin,
vinblastine, and dacarbazine, (3) cHL at high risk of relapse or
progression as post-autologous hematopoietic stem cell
transplantation (auto-HSCT) consolidation, (4) cHL after failure of
auto-HSCT or failure of at least two prior multi-agent chemotherapy
regimens in patients who are not auto-HSCT candidates, (5) sALCL
after failure of at least one prior multi-agent chemotherapy
regimen, and (6) primary cutaneous anaplastic large cell lymphoma
(pcALCL) or CD30-expressing mycosis fungoides (MF) who have
received prior systemic therapy.
Health Canada granted ADCETRIS approval with conditions in 2013
for patients with (1) HL after failure of autologous stem cell
transplant (ASCT) or after failure of at least two multi-agent
chemotherapy regimens in patients who are not ASCT candidates and
(2) sALCL after failure of at least one multi-agent chemotherapy
regimen. Non-conditional approval was granted for (3) post-ASCT
consolidation treatment of patients with HL at increased risk of
relapse or progression in 2017, (4) adult patients with pcALCL or
CD30-expressing MF who have received prior systemic therapy in
2018, (5) for previously untreated patients with Stage IV HL in
combination with doxorubicin, vinblastine, and dacarbazine in 2019,
and (6) for previously untreated adult patients with sALCL,
peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) or
angioimmunoblastic T-cell lymphoma (AITL), whose tumors express
CD30, in combination with cyclophosphamide, doxorubicin, prednisone
in 2019.
ADCETRIS received conditional marketing authorization from the
European Commission in October 2012. The approved indications in
Europe are: (1) for the treatment of 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, (2) for the treatment of
adult patients with relapsed or refractory sALCL, (3) for the
treatment of adult patients with CD30-positive Hodgkin lymphoma at
increased risk of relapse or progression following ASCT, (4) for
the treatment of adult patients with CD30-positive cutaneous T-cell
lymphoma (CTCL) after at least one prior systemic therapy and (5)
for the treatment of adult patients with previously untreated
CD30-positive Stage IV Hodgkin lymphoma in combination with AVD
(Adriamycin®, vinblastine and dacarbazine).
ADCETRIS has received marketing authorization by regulatory
authorities in 73 countries for relapsed or refractory Hodgkin
lymphoma and sALCL. See select important safety information,
including Boxed Warning, below.
Seattle Genetics and Takeda are jointly developing ADCETRIS.
Under the terms of the collaboration agreement, Seattle Genetics
has U.S. and Canadian commercialization rights and Takeda has
rights to commercialize ADCETRIS in the rest of the world. Seattle
Genetics 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.
About Seattle Genetics Seattle Genetics, Inc. is an
emerging multi-product, global biotechnology company that develops
and commercializes transformative therapies targeting cancer to
make a meaningful difference in people’s lives. ADCETRIS®
(brentuximab vedotin) utilizes the company’s industry-leading
antibody-drug conjugate (ADC) technology and is currently approved
for the treatment of multiple CD30-expressing lymphomas. Beyond
ADCETRIS, the company has a late-stage pipeline including
enfortumab vedotin for metastatic urothelial cancer, currently
being reviewed for approval by the FDA, and tisotumab vedotin in
clinical trials for metastatic cervical cancer, which utilize our
proprietary ADC technology. In addition, tucatinib, a small
molecule tyrosine kinase inhibitor, is in late-stage development
for HER2-positive metastatic breast cancer and in clinical
development for metastatic colorectal cancer. We are also
leveraging our expertise in empowered antibodies to build a
portfolio of proprietary immuno-oncology agents in clinical trials
targeting hematologic malignancies and solid tumors. The company is
headquartered in Bothell, Washington, and has a European office in
Switzerland. For more information on our robust pipeline, visit
www.seattlegenetics.com and follow @SeattleGenetics on Twitter.
ADCETRIS (brentuximab vedotin) 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 ADCETRIS concomitant with 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. Institute dose
modifications accordingly.
- 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 patients who receive
ADCETRIS in combination with chemotherapy for previously untreated
Stage III/IV cHL or previously untreated PTCL. 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 bacterial, fungal, or viral infections.
- Tumor lysis syndrome: Closely monitor patients with
rapidly proliferating tumor and high tumor burden.
- 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
compared to patients with normal renal function. 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 wasgreater in patients with moderate or severe hepatic
impairment compared to patients with normal hepatic function. 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
and death have been reported in ADCETRIS-treated patients. First
onset of symptoms occurred at various times from initiation of
ADCETRIS therapy, 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 preexisting 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 preexisting 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 antihyperglycemic 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 the potential risk to the fetus, and
to avoid pregnancy during ADCETRIS treatment and for at least 6
months after the final dose of ADCETRIS.
Most Common (≥20% in any study) Adverse Reactions:
Peripheral neuropathy, fatigue, nausea, diarrhea, neutropenia,
upper respiratory tract infection, pyrexia, constipation, vomiting,
alopecia, decreased weight, abdominal pain, anemia, stomatitis,
lymphopenia and mucositis.
Drug Interactions Concomitant use of strong CYP3A4
inhibitors or inducers has the potential to affect the exposure to
monomethyl auristatin E (MMAE).
Use in Specific Populations Moderate or severe hepatic
impairment or severe renal impairment: MMAE exposure and adverse
reactions are increased. Avoid use.
Advise males with female sexual partners of reproductive
potential to use effective contraception during ADCETRIS treatment
and for at least 6 months after the final dose of ADCETRIS.
Advise patients to report pregnancy immediately and avoid
breastfeeding while receiving ADCETRIS.
Please see the full Prescribing Information, including BOXED
WARNING, for ADCETRIS here.
Forward Looking Statements Certain of the statements made
in this press release are forward looking, such as those, among
others, relating to the potential uses and benefits of ADCETRIS
(brentuximab vedotin) in combination with OPDIVO® (nivolumab) in
frontline Hodgkin lymphoma (HL) patients age 60 years or older and
in relapsed or refractory classical HL under staggered and
concurrent dosing schedules, the therapeutic potential of ADCETRIS
in these indications and the company’s clinical development plans.
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 potential lack of efficacy
or risk of adverse events associated with the use of ADCETRIS in
certain clinical settings and the difficulty and uncertainty of
pharmaceutical product development. More information about the
risks and uncertainties faced by Seattle Genetics is contained
under the caption “Risk Factors” included in the company’s
Quarterly Report on Form 10-Q for the quarter ended September 30,
2019 filed with the Securities and Exchange Commission. Seattle
Genetics 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
law.
Opdivo® is a registered trademark of Bristol-Myers Squibb
Company.
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version on businesswire.com: https://www.businesswire.com/news/home/20191207005021/en/
Media: Monique Greer (425) 527-4641 mgreer@seagen.com
Investors: Peggy Pinkston (425) 527-4160
ppinkston@seagen.com
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