– Data Being Presented Underscore Commitment to Improving Patient
Outcomes and Care –
– Six Takeda Oncology-Sponsored Abstracts Accepted for Presentation
at ASCO 2018 and Eight Abstracts Accepted for Presentation at EHA 2018
CAMBRIDGE, Mass. & OSAKA, Japan–(BUSINESS WIRE)–Takeda Pharmaceutical Company Limited (TSE:
4502) today announced that the company will feature a total of 14
Takeda Oncology-sponsored presentations at two upcoming medical
meetings: the 54th Annual Meeting of the American Society of Clinical
Oncology (ASCO), June 1-5 in Chicago and the 23rd Congress of the
European Hematology Association (EHA), June 14-17 in Stockholm. This
year’s presentations will underscore Takeda’s unwavering pursuit to
advance hematologic cancer therapy and continue building upon research
in difficult-to-treat solid tumors.
“At ASCO and EHA we will present data, real-world findings and trial
updates on our pipeline assets as well as our marketed therapies,” said
Christophe Bianchi, M.D., President, Takeda Oncology. “At ASCO, we will
present updated Phase 2 ALTA trial results examining long-term efficacy
and safety of ALUNBRIG in patients with ALK+ non-small cell lung cancer
who are refractory to crizotinib. Notably, at EHA we will present data
on pre-specified subgroups from the ECHELON-1 Phase 3 trial evaluating a
combination with ADCETRIS as a frontline treatment for patients with
Hodgkin lymphoma. Takeda’s research continues to push innovation in
oncology to advance needed treatments and illustrates the company’s
vision to improve the lives of cancer patients.”
At this year’s ASCO meeting, updated Phase 2 ALTA (ALK in Lung
Cancer Trial of AP26113) trial results examining long-term
efficacy and safety of ALUNBRIG® (brigatinib) in a crizotinib
refractory anaplastic lymphoma kinase-positive (ALK+) non-small cell
lung cancer (NSCLC) population will be presented. During the poster
discussion presentations, TAK-788, a small molecule tyrosine kinase
inhibitor targeting the epidermal growth factor receptor (EGFR) and
human epidermal growth factor receptor 2 (HER2) mutations, including
exon 20 insertions, will report on the safety, pharmacokinetics and
preliminary antitumor activity of this molecule in NSCLC patients. In
addition, results from a first-in-human Phase 1 study of TAK-931, a
small molecule inhibitor of the CDC7 kinase activity, in patients with
advanced solid tumors will be shared during the oral presentations. The
trial, which investigates the effect of TAK-931 in up to 100
participants with solid tumors, examines the safety, tolerability and
pharmacokinetics of the oral medication to determine the maximum
The company also continues to deepen its scientific body of knowledge in
hematologic cancers. At ASCO, the company will present a “Trials in
Progress” poster on the ongoing randomized global Phase 3 trial, PANTHER
(investigational intravenous Pevonedistat plus Azacitidine
versus single-agent azacitidine as first-line Treatment for
patients with Higher-Risk myelodysplastic syndrome
(MDS), chronic myelomonocytic leukemia or low-blast acute myelogenous
Furthermore, at this year’s EHA meeting, data on the efficacy and safety
of a combination with ADCETRIS® (brentuximab vedotin) in
pre-specified subgroups with more advanced disease from the ECHELON-1
trial will be presented. Data demonstrate greater benefit across these
subgroups compared to the intent to treat population regardless of PET2
status based on the primary endpoint of modified progression-free
survival. In addition, encore data from the Phase 3 ECHELON-1 clinical
trial evaluating ADCETRIS as part of a frontline combination
chemotherapy regimen in previously untreated advanced stage Hodgkin
lymphoma will be featured. The data was previously presented in the
Plenary Session at the 59th American Society of Hematology (ASH) Annual
Meeting in December 2017. Finally, a study of TAK-659, a reversible dual
inhibitor of spleen tyrosine kinase (SYK) and FMS-like tyrosine kinase-3
(FLT3), in combination with standard of care treatments will present
preliminary safety and efficacy data in diffuse large B-cell lymphoma
Safety, efficacy and real-world use findings from Takeda
Oncology-sponsored trials examining a variety of blood cancers,
including lymphoma, multiple myeloma and MDS, will be featured at ASCO
and / or EHA.
The six Takeda Oncology-sponsored abstracts accepted for presentation
during ASCO 2018 and eight abstracts at EHA 2018 include:
ASCO Annual Meeting 2018
Note: All times listed are in Central Daylight Time
ADCETRIS (brentuximab vedotin)
Vedotin with Chemotherapy for Stage III or IV Hodgkin Lymphoma (HL):
Impact of Cycle 2 PET Result on Modified Progression-Free Survival.
Abstract 7539. Monday, June 4, 8:00-11:30 a.m., Hall A.
Outcomes with Brentuximab Vedotin (BV) plus Chemotherapy in Patients
with Newly Diagnosed Advanced Stage Hodgkin Lymphoma. Abstract
7534. Monday, June 4, 8:00-11:30 a.m., Hall A.
(BRG) in Crizotinib (CRZ)-Refractory ALK+ Non–Small Cell Lung Cancer
(NSCLC): Efficacy Updates and Exploratory Analysis of CNS ORR and
Overall ORR by Baseline (BL) Brain Lesion Status. Abstract 9061.
Sunday, June 3, 8:00-11:30 a.m., Hall A.
Phase 1 Study of TAK-931, an Oral Cell Division Cycle 7 (CDC7)
Inhibitor in Patients (Pts) with Advanced Solid Tumors. Abstract
2506. Oral presentation. Friday, June 1, 4:09-4:21 p.m., S406.
Report of Safety, PK and Preliminary Antitumor Activity of the Oral
EGFR/HER2 Exon 20 Inhibitor TAK-788 (AP32788) in Non–Small Cell Lung
Cancer (NSCLC). Abstract 9015. Sunday, June 3, 11:30 a.m.-12:45
p.m., Hall A.
3 Study of First Line Pevonedistat (PEV) + Azacitidine (AZA) versus
Single-Agent AZA in Patients with Higher-Risk Myelodysplastic
Syndromes (HR MDS), Chronic Myelomonocytic Leukemia (CMML) or
Low-Blast Acute Myelogenous Leukemia (AML). Abstract TPS7077.
Monday, June 4, 8:00-11:00 a.m., Hall A.
EHA 23rd Congress
Note: All times listed are in Central European Time
ADCETRIS (brentuximab vedotin)
Vedotin Plus Chemotherapy in High Risk Advanced-Stage Classical
Hodgkin Lymphoma (CHL) Patients: Results of Pre-Specified Sub-Group
Analyses from the ECHELON-1 Study. Abstract S112. Oral
presentation. Friday, June 15, 12:00-12:15 p.m., Room A2.
Vedotin with Chemotherapy for Stage III or IV Hodgkin Lymphoma: Impact
of Cycle2 PET Modified Progression-Free Survival. Abstract PS1172.
Saturday, June 16, 5:30-7:00 p.m., Poster Area.
Brentuximab Vedotin Plus Chemotherapy Exhibits Superior Modified
Progression-Free Survival vs Chemotherapy Alone in Patients with Stage
III or IV Hodgkin Lymphoma: Phase 3 ECHELON-1 Study. Abstract
PS1182. Saturday, June 16, 5:30-7:00p.m., Poster Area.
Vedotin in Relapsed/Refractory Systemic Anaplastic Large-Cell
Lymphoma: A Cost-Effectiveness Analysis. Abstract PF684. Friday,
June 15, 5:30-7:00 p.m., Poster Area.
Global Treatment Standard in Multiple Myeloma (MM) Remains Elusive
Despite Advances in Care Over 15 Years: First Results from INSIGHT MM,
the Largest Global Prospective, Observational MM Study. Abstract
PS1300. Saturday, June 16, 5:30-7:00 p.m., Poster Area
Clinical Trial (RCT) Representativeness & Outcomes in
Relapsed/Refractory Multiple Myeloma (RRMM) Real World (RW) Patients:
Comparison of ASPIRE, TOURMALINE-MM1, POLLUX & ELOQUENT RCTS.
Abstract PS1336. Saturday, June 16, 5:30-7:00 p.m., Poster Area.
1/1b Study of Pevonedistat (PEV) as a Single Agent or Combined with
Azacitidine (AZA) in East Asian Patients (Pts) with Acute Myeloid
Leukemia (AML) or Myelodysplastic Syndrome (MDS). Abstract PS997.
Saturday, June 16, 5:30-7:00 p.m., Poster Area.
Plus Bendamustine (+/-Rituximab), Gemcitabine, Lenalidomide or
Ibrutinib in Patients (Pts) with Advanced Non-Hodgkin Lymphoma (NHL).
Abstract PF281. Friday, June 15, 5:30-7:00 p.m., Poster Area.
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-positive tumor cells.
ADCETRIS injection for intravenous infusion has received FDA regular
approval for five indications in adult patients with: (1) previously
untreated Stage III or IV classical Hodgkin lymphoma (cHL), in
combination with chemotherapy, (2) cHL at high risk of relapse or
progression as post-autologous hematopoietic stem cell transplantation
(auto-HSCT) consolidation, (3) 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, (4) sALCL after failure of at least one
prior multi-agent chemotherapy regimen, and (5) 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 for relapsed or
refractory Hodgkin lymphoma and sALCL in 2013, and non-conditional
approval for post-autologous stem cell transplant (ASCT) consolidation
treatment of Hodgkin lymphoma patients at increased risk of relapse or
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) 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, and (4) for the treatment of adult patients with CD30-positive
cutaneous T-cell lymphoma (CTCL) after at least one prior systemic
ADCETRIS has received marketing authorization by regulatory authorities
in more than 70 countries for relapsed or refractory Hodgkin lymphoma
and sALCL. See important safety information below.
ADCETRIS is being evaluated broadly in more than 70 clinical trials,
including a Phase 3 study in frontline Hodgkin lymphoma (ECHELON-1) and
another Phase 3 study in frontline CD30-positive peripheral T-cell
lymphomas (ECHELON-2), as well as trials in many additional types of
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.
ADCETRIS (brentuximab vedotin) Important Safety Information (European
Please refer to Summary of Product Characteristics
(SmPC) before prescribing.
ADCETRIS is contraindicated for patients
with hypersensitivity to brentuximab vedotin and its excipients. In
addition, combined use of ADCETRIS with bleomycin causes pulmonary
SPECIAL WARNINGS & PRECAUTIONS
Progressive multifocal leukoencephalopathy (PML): John Cunningham
virus (JCV) reactivation resulting in progressive multifocal
leukoencephalopathy (PML) and death can occur in patients treated with
ADCETRIS. PML has been reported in patients who received ADCETRIS after
receiving multiple prior chemotherapy regimens. PML is a rare
demyelinating disease of the central nervous system that results from
reactivation of latent JCV and is often fatal.
Closely monitor patients for new or worsening neurological, cognitive,
or behavioral signs or symptoms, which may be suggestive of PML.
Suggested evaluation of PML includes neurology consultation,
gadolinium-enhanced magnetic resonance imaging of the brain, and
cerebrospinal fluid analysis for JCV DNA by polymerase chain reaction or
a brain biopsy with evidence of JCV. A negative JCV PCR does not exclude
PML. Additional follow up and evaluation may be warranted if no
alternative diagnosis can be established Hold dosing for any suspected
case of PML and permanently discontinue ADCETRIS if a diagnosis of PML
Be alert to PML symptoms that the patient may not notice (e.g.,
cognitive, neurological, or psychiatric symptoms).
Pancreatitis: Acute pancreatitis has been observed in
patients treated with ADCETRIS. Fatal outcomes have been reported.
Closely monitor patients for new or worsening abdominal pain, which may
be suggestive of acute pancreatitis. Patient evaluation may include
physical examination, laboratory evaluation for serum amylase and serum
lipase, and abdominal imaging, such as ultrasound and other appropriate
diagnostic measures. Hold ADCETRIS for any suspected case of acute
pancreatitis. ADCETRIS should be discontinued if a diagnosis of acute
pancreatitis is confirmed.
Pulmonary Toxicity: Cases of pulmonary toxicity, some with
fatal outcomes, including pneumonitis, interstitial lung disease, and
acute respiratory distress syndrome (ARDS), have been reported in
patients receiving ADCETRIS. Although a causal association with ADCETRIS
has not been established, the risk of pulmonary toxicity cannot be ruled
out. Promptly evaluate and treat new or worsening pulmonary symptoms
appropriately. Consider holding dosing during evaluation and until
Serious infections and opportunistic infections: Serious
infections such as pneumonia, staphylococcal bacteremia, sepsis/septic
shock (including fatal outcomes), and herpes zoster, and opportunistic
infections such as Pneumocystis jiroveci pneumonia and
oral candidiasis have been reported in patients treated with ADCETRIS.
Carefully monitor patients during treatment for emergence of possible
serious and opportunistic infections.
Infusion-related reactions (IRR): Immediate and delayed IRR, as
well as anaphylaxis, have occurred with ADCETRIS. Carefully monitor
patients during and after an infusion. If anaphylaxis occurs,
immediately and permanently discontinue administration of ADCETRIS
Appropriate medical therapy should be administered. If an IRR occurs,
interrupt the infusion and institute appropriate medical management. The
infusion may be restarted at a slower rate after symptom resolution.
Patients who have experienced a prior IRR should be premedicated for
subsequent infusions. IRRs are more frequent and more severe in patients
with antibodies to ADCETRIS.
Tumor lysis syndrome (TLS): TLS has been reported with ADCETRIS.
Patients with rapidly proliferating tumor and high tumor burden are at
risk of TLS. Monitor these patients closely and managed according to
best medical practice.
Peripheral neuropathy (PN): ADCETRIS treatment may cause PN,
both sensory and motor. ADCETRIS-induced PN is typically cumulative and
reversible in most cases. Monitor patients for symptoms of PN, such as
hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning
sensation, neuropathic pain, or weakness. Patients experiencing new or
worsening PN may require a delay and a dose reduction or discontinuation
Hematological toxicities: Grade 3 or Grade 4 anemia,
thrombocytopenia, and prolonged (equal to or greater than one week)
Grade 3 or Grade 4 neutropenia can occur with ADCETRIS. Monitor complete
blood counts prior to administration of each dose.
Febrile neutropenia: Febrile neutropenia has been reported.
Closely monitor patients for fever and manage according to best medical
practice if febrile neutropenia develops.
Stevens-Johnson syndrome (SJS): SJS and toxic epidermal
necrolysis (TEN) have been reported with ADCETRIS. Fatal outcomes have
been reported. Discontinue treatment with ADCETRIS if SJS or TEN occurs
and administer appropriate medical therapy.
Gastrointestinal (GI) Complications: GI complications, some with
fatal outcomes, including intestinal obstruction, ileus, enterocolitis,
neutropenic colitis, erosion, ulcer, perforation and haemorraghe, have
been reported. Promptly evaluate and treat patients if new or worsening
GI symptoms occur.
Hepatotoxicity: Elevations in alanine aminotransferase (ALT)
and aspartate aminotransferase (AST) have been reported. Serious cases
of hepatotoxicity, including fatal outcomes, have also occurred. Test
liver function prior to treatment initiation and routinely monitor
patients receiving ADCETRIS for liver elevations. Patients experiencing
hepatotoxicity may require a delay, dose modification, or
discontinuation of ADCETRIS.
Hyperglycemia: Hyperglycemia has been reported during trials in
patients with an elevated body mass index (BMI) with or without a
history of diabetes mellitus. Closely monitor serum glucose for patients
who experiences an event of hyperglycemia. Administer anti-diabetic
treatment as appropriate.
Renal and Hepatic Impairment: There is limited experience in
patients with renal and hepatic impairment. Available data indicate that
MMAE clearance might be affected by severe renal impairment, hepatic
impairment, and by low serum albumin concentrations.
CD30+ CTCL: The size of the treatment effect in CD30 + CTCL
subtypes other than mycosis fungoides (MF) and primary cutaneous
anaplastic large cell lymphoma (pcALCL) is not clear due to lack of high
level evidence. In two single arm phase II studies of ADCETRIS, disease
activity has been shown in the subtypes Sézary syndrome (SS),
lymphomatoid papulosis (LyP) and mixed CTCL histology. These data
suggest that efficacy and safety can be extrapolated to other CTCL CD30+
subtypes. Carefully consider the benefit-risk per patient and use
caution in other CD30+ CTCL patient types.
Sodium content in excipients: ADCETRIS contains a maximum of 2.1
mmol (or 47 mg) of sodium per dose. Take this into consideration for
patients on a controlled sodium diet.
Patients who are receiving a strong CYP3A4 and
P-gp inhibitor, concomitantly with ADCETRIS may have an increased risk
of neutropenia and should be closely monitored. Co-administration of
ADCETRIS with a CYP3A4 inducer did not alter the plasma exposure of
ADCETRIS but it appeared to reduce plasma concentrations of MMAE
metabolites that could be assayed. ADCETRIS is not expected to alter the
exposure to drugs that are metabolized by CYP3A4 enzymes.
PREGNANCY: Advise women of childbearing potential to use two
methods of effective contraception during treatment with ADCETRIS and
until 6 months after treatment. There are no data from the use of
ADCETRIS in pregnant women, although studies in animals have shown
reproductive toxicity. Do not use ADCETRIS during pregnancy unless the
benefit to the mother outweighs the potential risks to the fetus.
LACTATION (breast-feeding): There are no data as to whether
ADCETRIS or its metabolites are excreted in human milk, therefore a risk
to the newborn/infant cannot be excluded. With the potential risk, a
decision should be made whether to discontinue breast-feeding or
discontinue/abstain from therapy with ADCETRIS.
FERTILITY: In nonclinical studies, ADCETRIS treatment has
resulted in testicular toxicity, and may alter male fertility. Advise
men being treated with ADCETRIS not to father a child during treatment
and for up to 6 months following the last dose.
Effects on ability to drive and use machines: ADCETRIS may have a
minor influence on the ability to drive and use machines.
The most frequent adverse reactions
(≥10%) were infections, peripheral sensory neuropathy, nausea, fatigue,
diarrhoea, pyrexia, upper respiratory tract infection, neutropenia,
rash, cough, vomiting, arthralgia, peripheral motor neuropathy,
infusion-related reactions, pruritus, constipation, dyspnoea, weight
decreased, myalgia and abdominal pain.
Serious adverse drug reactions were: pneumonia, acute respiratory
distress syndrome, headache, neutropenia, thrombocytopenia,
constipation, diarrhea, vomiting, nausea, pyrexia, peripheral motor
neuropathy, peripheral sensory neuropathy, hyperglycemia, demyelinating
polyneuropathy, tumor lysis syndrome, and Stevens-Johnson syndrome.
Serious adverse drug reactions occurred in 12% of patients. The
frequency of unique serious adverse drug reactions was ≤1%.
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 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
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: Prolonged (≥1 week) severe neutropenia
and Grade 3 or 4 thrombocytopenia or anemia can occur with ADCETRIS.
Febrile neutropenia has been reported with ADCETRIS. Monitor complete
blood counts prior to each ADCETRIS dose. Consider more frequent
monitoring 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
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 was greater in patients with moderate or severe hepatic
impairment compared to patients with normal hepatic function.
Takeda Pharmaceutical Company Limited
Kobayashi, +81 (0) 3-3278-2095
Kate Burd, +44 7974 151510
Sara Noonan, +1-617-551-3683