- 96 Percent Complete Remission Rate in Newly Diagnosed Hodgkin
Lymphoma Patients Treated with ADCETRIS in Combination with AVD
Chemotherapy -
- Safety and Response Data Support Ongoing Phase III Trial of
ADCETRIS and AVD Chemotherapy in Patients with Newly Diagnosed Hodgkin
Lymphoma -
ATLANTA--(BUSINESS WIRE)--Dec. 10, 2012--
Seattle Genetics, Inc. (Nasdaq:SGEN) today announced results from a
phase I clinical trial of ADCETRIS (brentuximab vedotin) in combination
with chemotherapy for the treatment of newly diagnosed advanced stage
Hodgkin lymphoma (HL) patients. The data were presented at the 54th
American Society of Hematology (ASH) Annual Meeting and Exposition being
held December 8-11, 2012 in Atlanta, GA. ADCETRIS is an antibody-drug
conjugate (ADC) directed to CD30, a defining marker of classical HL.
ADCETRIS is currently not approved for use in the front-line treatment
of HL.
In the phase I trial, newly diagnosed patients received ADCETRIS
concomitantly with either ABVD (Adriamycin, bleomycin, vinblastine and
dacarbazine) or AVD, which removes bleomycin from the regimen. At the
end of front-line therapy, 24 of 25 patients (96 percent) treated with
ADCETRIS plus AVD and 21 of 22 (95 percent) patients treated with
ADCETRIS plus ABVD had a complete remission. None of the patients
treated in the ADCETRIS plus AVD cohort experienced pulmonary toxicity,
compared with an expected rate of pulmonary toxicity caused by ABVD
alone of 10-25 percent. The trial was designed to establish the safety
profile and maximum tolerated dose when adding ADCETRIS to ABVD or AVD.
Antitumor activity was assessed as a secondary endpoint.
"For over 30 years, the standard of care for front-line HL has been a
chemotherapy regimen called ABVD that has demonstrated a complete
remission rate of 70 to 80 percent and is associated with considerable
life-threatening toxicities. There is a significant need to identify
better treatment options for patients in the front-line HL setting,”
said Clay B. Siegall, Ph.D., President and Chief Executive Officer of
Seattle Genetics. "Our goal is to redefine front-line treatment of HL
with the addition of ADCETRIS, and the encouraging results of this phase
I trial clearly support this goal and provide rationale for the ongoing
ADCETRIS phase III trial in this setting."
Front-line Therapy with Brentuximab Vedotin Combined with ABVD or AVD
in Patients with Newly Diagnosed Advanced Stage Hodgkin Lymphoma
(Abstract #798)
In this open-label, multicenter trial, cohorts of patients received an
escalating dose of ADCETRIS (0.6 milligrams per kilogram (mg/kg), 0.9
mg/kg, 1.2 mg/kg) every two weeks concomitantly with ABVD or a dose of
1.2 mg/kg every two weeks concomitantly with AVD.
Fifty-one patients were enrolled in the phase I study and 47 were
evaluable for response at trial completion. The 47 evaluable patients
included 25 in the ADCETRIS plus AVD cohort and 22 in the ADCETRIS plus
ABVD cohorts. All patients were previously untreated and 45 percent had
Stage IV HL. The median age of patients across all cohorts of the trial
was 33 years. Key findings, which were highlighted in an oral
presentation by Dr. Stephen Ansell, Professor of Medicine, Division of
Hematology, from the Mayo Clinic, included:
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Among the 25 evaluable patients in the ADCETRIS plus AVD cohort, 24
patients (96 percent) who completed front-line therapy on study
achieved a complete remission and one patient (four percent)
experienced disease progression.
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Among the 22 evaluable patients in the ADCETRIS plus ABVD cohorts, 21
patients (95 percent) who completed front-line therapy on study
achieved a complete remission. One patient was not evaluable for
response due to adverse events.
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Of the 48 evaluable patients in both study arms, 24 out of 26 (92
percent) in the AVD cohort and 22 out of 22 (100 percent) in the ABVD
cohorts had negative interim PET scans after Cycle 2 as assessed by
central review.
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No dose-limiting toxicity was observed at the maximum planned dose of
ADCETRIS (1.2 mg/kg every two weeks).
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The most common adverse events noted in the ABVD and AVD cohorts,
respectively, were nausea (72 percent, 85 percent), neutropenia (80
percent, 77 percent), peripheral sensory neuropathy (72 percent, 73
percent), vomiting (60 percent, 42 percent) and fatigue (44 percent,
50 percent).
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Grade 3 or higher adverse events occurring in more than one patient
overall noted in the ABVD and AVD cohorts, respectively, were
neutropenia (80 percent, 77 percent), anemia (20 percent, 12 percent),
febrile neutropenia (20 percent, 8 percent) and pulmonary toxicity (24
percent, 0 percent). One patient experienced a Grade 3 peripheral
neuropathy event.
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As previously reported in the interim analysis of this study,
pulmonary toxicity was seen in the ADCETRIS plus ABVD cohorts,
resulting in a contraindication for the concomitant administration of
ADCETRIS and bleomycin. No pulmonary toxicity was observed in the
ADCETRIS plus AVD cohort. In the ADCETRIS plus ABVD cohorts, 11 out of
25 patients (44 percent) had a pulmonary toxicity event, and events
were resolved in nine of 11 patients (82 percent).
“For decades researchers have strived to improve our front-line HL
treatment strategy by enhancing the activity of traditional chemotherapy
regimens while reducing the significant toxicities and long-term side
effects of such regimens,” said Stephen Ansell, M.D., Ph.D., Professor
of Medicine, Division of Hematology, Mayo Clinic. “There is a
significant need to identify better treatment options for patients in
the front-line setting. With a complete response rate of 96 percent and
a manageable safety profile, data from this trial support further
evaluation of ADCETRIS administered concomitantly with AVD in previously
untreated HL patients to potentially improve the current standard of
care.”
Seattle Genetics and Millennium: The Takeda Oncology Company have
initiated a phase III clinical trial in advanced stage front-line HL
patients. The randomized trial is comparing progression-free survival in
patients receiving ADCETRIS in combination with AVD to patients
receiving ABVD alone. For more information about the trial visit www.seattlegenetics.com
or www.clinicaltrials.gov.
About ADCETRIS
ADCETRIS (brentuximab vedotin) 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 received accelerated approval from the U.S. Food and Drug
Administration (FDA) in August 2011 for two indications: (1) the
treatment of patients with Hodgkin lymphoma after failure of autologous
stem cell transplant (ASCT) or after failure of at least two prior
multi-agent chemotherapy regimens in patients who are not ASCT
candidates, and (2) the treatment of patients with systemic anaplastic
large cell lymphoma (sALCL) after failure of at least one prior
multi-agent chemotherapy regimen. The indications for ADCETRIS are based
on response rate. There are no data available demonstrating improvement
in patient-reported outcomes or survival with ADCETRIS.
ADCETRIS was granted conditional marketing authorization by the European
Commission in October 2012 for the treatment of adult patients with
relapsed or refractory CD30+ HL: (1) following autologous stem cell
transplant (ASCT), or (2) following at least two prior therapies when
ASCT or multi-agent chemotherapy is not a treatment option. ADCETRIS is
indicated for the treatment of adult patients with relapsed or
refractory systemic anaplastic large cell lymphoma (sALCL). See
important safety information below.
Seattle Genetics and Millennium are jointly developing ADCETRIS. Under
the terms of the collaboration agreement, Seattle Genetics has U.S. and
Canadian commercialization rights and the Takeda Group has rights to
commercialize ADCETRIS in the rest of the world. Seattle Genetics and
the Takeda Group are funding joint development costs for ADCETRIS on a
50:50 basis, except in Japan where the Takeda Group will be solely
responsible for development costs.
About 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. 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
generally expresses CD30.
About Seattle Genetics
Seattle Genetics is a biotechnology company focused on the development
and commercialization of monoclonal antibody-based therapies for the
treatment of cancer. The U.S. Food and Drug Administration granted
accelerated approval of ADCETRIS in August 2011 for two indications.
ADCETRIS is being developed in collaboration with Millennium: The Takeda
Oncology Company. In addition, Seattle Genetics has three other
clinical-stage ADC programs: SGN-75, ASG-5ME and ASG-22ME. Seattle
Genetics has collaborations for its ADC technology with a number of
leading biotechnology and pharmaceutical companies, including Abbott,
Agensys (an affiliate of Astellas), Bayer, Celldex Therapeutics, Daiichi
Sankyo, Genentech, GlaxoSmithKline, Millennium, Pfizer and Progenics, as
well as ADC co-development agreements with Agensys and Genmab. More
information can be found at www.seattlegenetics.com.
U.S. Important Safety Information
BOXED WARNING
Progressive multifocal leukoencephalopathy (PML): JC virus infection
resulting in PML and death can occur in patients receiving ADCETRIS.
Contraindication:
Concomitant use of ADCETRIS and bleomycin is contraindicated due to
pulmonary toxicity.
Warnings and Precautions:
-
Peripheral neuropathy: ADCETRIS treatment causes a peripheral
neuropathy that is predominantly sensory. Cases of peripheral motor
neuropathy have also been reported. ADCETRIS-induced peripheral
neuropathy is cumulative. Treating physicians should monitor patients
for symptoms of neuropathy, such as hypoesthesia, hyperesthesia,
paresthesia, discomfort, a burning sensation, neuropathic pain or
weakness and institute dose modifications accordingly.
-
Infusion reactions: Infusion-related reactions, including anaphylaxis,
have occurred with ADCETRIS. Monitor patients during infusion. If an
infusion reaction occurs, the infusion should be interrupted and
appropriate medical management instituted. If anaphylaxis occurs, the
infusion should be immediately and permanently discontinued and
appropriate medical management instituted.
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Neutropenia: Monitor complete blood counts prior to each dose of
ADCETRIS and consider more frequent monitoring for patients with Grade
3 or 4 neutropenia. If Grade 3 or 4 neutropenia develops, manage by
dose delays, reductions or discontinuation. Prolonged (≥1 week) severe
neutropenia can occur with ADCETRIS.
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Tumor lysis syndrome: Patients with rapidly proliferating tumor and
high tumor burden are at risk of tumor lysis syndrome and these
patients should be monitored closely and appropriate measures taken.
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Progressive multifocal leukoencephalopathy (PML): JC virus infection
resulting in PML and death has been reported in ADCETRIS-treated
patients. In addition to ADCETRIS therapy, other possible contributory
factors include prior therapies and underlying disease that may cause
immunosuppression. Consider the diagnosis of PML in any patient
presenting with new-onset signs and symptoms of central nervous system
abnormalities. Evaluation of PML includes, but is not limited to,
consultation with a neurologist, brain MRI, and lumbar puncture or
brain biopsy. Hold ADCETRIS if PML is suspected and discontinue
ADCETRIS if PML is confirmed.
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Stevens-Johnson syndrome: Stevens-Johnson syndrome has been reported
with ADCETRIS. If Stevens-Johnson syndrome occurs, discontinue
ADCETRIS and administer appropriate medical therapy.
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Use in pregnancy: Fetal harm can occur. Pregnant women should be
advised of the potential hazard to the fetus.
Adverse Reactions:
ADCETRIS was studied as monotherapy in 160 patients in two phase 2
trials. Across both trials, the most common adverse reactions (≥20%),
regardless of causality, were neutropenia, peripheral sensory
neuropathy, fatigue, nausea, anemia, upper respiratory tract infection,
diarrhea, pyrexia, rash, thrombocytopenia, cough and vomiting.
Drug Interactions:
Patients who are receiving strong CYP3A4 inhibitors concomitantly with
ADCETRIS should be closely monitored for adverse reactions.
For additional important safety information, including Boxed WARNING,
please see the full U.S. prescribing information for ADCETRIS at www.seattlegenetics.com
or www.ADCETRIS.com.
Certain of the statements made in this press release are forward
looking, such as those, among others, relating to the therapeutic
potential of ADCETRIS in the featured indication and initiation of
future clinical trials. 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 the
inability to show sufficient activity in the phase III trial and the
risk of adverse events as ADCETRIS advances in clinical trials. In
addition, data from our clinical trials, including our pivotal trials
which were the basis for FDA accelerated approval, may not necessarily
be indicative of subsequent clinical trial results. More information
about the risks and uncertainties faced by Seattle Genetics is contained
in the company’s 10-Q for the quarter ended September 30, 2012 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.
Source: Seattle Genetics, Inc.
Seattle Genetics, Inc.
Investors:
Peggy Pinkston,
+1-425-527-4160
ppinkston@seagen.com
or
Media:
Tricia
Larson, +1-425-527-4180
tlarson@seagen.com
