–
First Presentation of Interim Phase 1/2 Data Reported in Pediatric
Patients with Relapsed or Refractory Hodgkin Lymphoma or relapsed or
refractory Systemic Anaplastic Large Cell Lymphoma -
CHICAGO & OSAKA, Japan - Saturday, June 1st 2013 [ME NewsWire]
2013 ASCO Annual Meeting
(BUSINESS
WIRE)-- Takeda Pharmaceutical Company Limited (TSE:4502) today
announced interim data from a Phase 1/2, open-label, multicenter study
with ADCETRIS® (brentuximab vedotin) in pediatric patients diagnosed
with CD30-positive relapsed or refractory Hodgkin lymphoma (HL) or
relapsed or refractory systemic anaplastic large cell lymphoma (sALCL).
Data were presented from the Phase 1 portion of the study, which
evaluated the safety, maximum tolerated dose (MTD) and/or recommended
Phase 2 dose (RP2D), and pharmacokinetics (PK) of ADCETRIS. The results
were reported during a poster presentation at the American Society of
Clinical Oncology (ASCO) Annual Meeting held May 31 – June 4, 2013 in
Chicago, IL.
ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL and sALCL.
“This
is the first clinical trial examining the use of ADCETRIS in pediatric
patients,” said Kathleen Neville, M.D., M.S., Director, Experimental
Therapeutics in Pediatric Cancer, Children’s Mercy Hospitals and
Clinics, Kansas City, MO. “There is an unmet medical need for children
diagnosed with relapsed or refractory HL or relapsed or refractory
sALCL. We are encouraged by these early results and look forward to
reporting data from the Phase 2 portion of the study when they are
available.”
Phase I/II Study of Brentuximab Vedotin in Pediatric
Patients with Relapsed or Refractory Hodgkin Lymphoma or Systemic
Anaplastic Large Cell Lymphoma: Interim Phase I Safety Data
The
poster presentation featured interim data from the Phase 1 portion of
the study, which evaluated 12 pediatric patients aged 2 to <18 and="" assessment.="" br="" complete="" endpoint="" endpoints="" facility="" hl="" included="" independent="" mtd="" or="" overall="" partial="" pediatric="" per="" pk.="" primary="" rate="" refractory="" relapsed="" remission="" reported="" response="" review="" rp2d="" safety="" salcl.="" secondary="" that="" the="" was="" were="" with="" years="">
Data, presented by Anna R.K. Franklin, M.D., Children's Cancer Hospital, MD Anderson Cancer Center, Houston, TX., included:
The RP2D for pediatric patients was determined to be 1.8 milligrams/kilogram (mg/kg) on an every three week basis
The most common treatment-emergent adverse events (TEAEs) ≥ Grade 2
were nausea (8 patients), pyrexia (6 patients), upper abdominal pain (4
patients) and paresthesia (4 patients)
Seven serious AEs (SAEs)
of ≥ Grade 3 were reported in 6 patients (50 percent) at 1.8 mg/kg,
including pyrexia unrelated to treatment (1 patient), hepatotoxicity and
febrile neutropenia (1 patient), anaphylactic reaction (1 patient),
supraventricular tachycardia unrelated to treatment (1 patient), pain in
extremity (1 patient), and cardiac arrest resulting in death unrelated
to treatment (1 patient)
Two patients who received 1.8 mg/kg of ADCETRIS discontinued treatment due to a drug-related SAE
PK analyses showed dose-dependent exposure and MMAE release time typical of ADCs
The ORR of 8 evaluable patients who received the RP2D was 88 percent; the CR rate was 38 percent
The
median age of the patients was 14.5 years. Ten patients were diagnosed
with relapsed or refractory HL and two patients were diagnosed with
relapsed or refractory sALCL. Participants received a median of 7 cycles
(range, 1–14) of ADCETRIS by intravenous infusion once every 21 days
starting with 1.4 mg/kg escalating to 1.8 mg/kg.
Details of the poster presentation are as follows:
Poster session on June 1, 2013 at 1:15 PM CT
Poster discussion on June 1, 2013 from 4:45 PM – 5:45 PM CT in Hall S A2
Poster: #36C
First author: Kathleen Neville, M.D., Children’s Mercy Hospital Hematology/Oncology, Kansas City, MO
This
clinical trial is part of the Pediatric Investigational Plan approved
by the Pediatric Committee of the European Medicines Agency. The Phase 2
portion of the study is ongoing and results will be presented at a
later date. For more information about the trial please visit
www.clinicaltrials.gov.
About ADCETRIS® (brentuximab vedotin)
ADCETRIS® (brentuximab vedotin) is the first and only targeted CD30
antibody-drug conjugate (ADC) being evaluated in a variety of
CD30-expressing malignancies including Hodgkin lymphoma (HL) and
systemic anaplastic large cell lymphoma (sALCL). The ADC utilizes
Seattle Genetics’ proprietary technology, which employs a linker system
designed to be stable in the bloodstream but to release monomethyl
auristatin E (MMAE) upon internalization into CD30-expressing tumor
cells.
ADCETRIS was granted conditional marketing authorization
by the European Commission in October 2012 for the treatment of adult
patients with relapsed or refractory CD30-positive 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 sALCL. ADCETRIS also received marketing
authorization by regulatory authorities in Switzerland and Korea.
ADCETRIS
was granted accelerated approval by the U.S. Food and Drug
Administration (FDA) in August 2011 for two indications: (1) the
treatment of patients with HL 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 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.
Millennium:
The Takeda Oncology Company and Seattle Genetics 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 is 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 expresses CD30.
About Anaplastic Large Cell
Lymphoma ALCL is a type of aggressive T-cell lymphoma, comprising about 3
percent of all non-Hodgkin lymphomas (NHL) in adults and between 10 and
30 percent of all NHL in children. There are two distinct forms/types
of ALCL, including primary cutaneous ALCL and systemic ALCL (sALCL).
sALCL is a clinically aggressive, systemic lymphoma that primarily
involves lymph nodes.
About Takeda Located in Osaka, Japan,
Takeda is a research-based global company with its main focus on
pharmaceuticals. As the largest pharmaceutical company in Japan and one
of the global leaders of the industry, Takeda is committed to strive
towards better health for people worldwide through leading innovation in
medicine. Additional information about Takeda is available through its
corporate website, www.takeda.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.
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.
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.
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.
Stevens-Johnson
syndrome: Stevens-Johnson syndrome has been reported with ADCETRIS. If
Stevens-Johnson syndrome occurs, discontinue ADCETRIS and administer
appropriate medical therapy.
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.ADCETRIS.com.
Editor’s Note: This press release
is also available under the Media section of the Company’s website at:
www.millennium.com/InTheNews.aspx.
Contacts
Millennium
Lindsay Treadway, +1-617-444-3383
lindsay.treadway@mpi.com
Takeda Pharmaceutical Company Limited
Corporate Communications Dept. (PR/IR)
+81-3-3278-2037
18>
No comments:
Post a Comment