− TOURMALINE-MM2 Data Presented Virtually at the Society of Hematologic Oncology (SOHO) Eighth Annual Meeting
CAMBRIDGE, Mass. & OSAKA, Japan-Monday 14 September 2020 [ AETOS Wire ]
(BUSINESS
WIRE) -- Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK)
(“Takeda”) today announced results from the Phase 3 TOURMALINE-MM2 trial
evaluating the addition of NINLARO™ (ixazomib) to lenalidomide and
dexamethasone versus lenalidomide and dexamethasone plus placebo in
newly diagnosed multiple myeloma patients not eligible for autologous
stem cell transplant. These data will be presented at the virtual
scientific meeting of the Society of Hematologic Oncology (SOHO) on
Wednesday, September 9, 2020 at 6:15 p.m. CT.
The study found the
addition of NINLARO to lenalidomide and dexamethasone resulted in a
13.5 month increase in median progression-free survival (PFS) (35.3
months in the NINLARO arm, compared to 21.8 months in the placebo arm;
hazard ratio [HR] 0.830; p=0.073). The trial did not meet the threshold
for statistical significance and the primary endpoint of PFS was not
met.
“There is a specific need in newly diagnosed multiple
myeloma, given there are currently no approved all-oral, proteasome
inhibitor-based treatment options,” said Thierry Facon, MD, Lille
University Hospital, principal investigator and lead author of
TOURMALINE-MM2. “Findings from the TOURMALINE-MM2 trial are important
overall for this patient population as well as across multiple subgroups
including patients with high-risk cytogenetics. We hope these data will
help inform future research and further progress for the multiple
myeloma community.”
Other endpoints presented include complete
response (CR) rate, overall survival (OS) and median time to progression
(TTP). The safety profile associated with NINLARO from the trial was
generally consistent with the existing prescribing information.
“We
hope the findings from the TOURMALINE-MM2 trial will encourage
constructive conversations and help progress future research efforts,
particularly for patients who could benefit from an all-oral, proteasome
inhibitor-based combination that helps preserve quality of life,” said
Christopher Arendt, Head, Oncology Therapeutic Area Unit, Takeda. “As a
company, we remain committed to the multiple myeloma community and look
forward to sharing mature data from our ongoing Phase 3 multiple myeloma
maintenance studies in the future.”
Key findings to be presented by TOURMALINE-MM2 trial investigator, Shaji Kumar, MD, Mayo Clinic, include:
Median PFS in the NINLARO arm was 35.3 months compared to 21.8 months in the placebo arm (HR 0.830; p=0.073).
In the prespecified expanded high-risk cytogenetics subgroup, median
PFS was 23.8 months in the NINLARO arm versus 18.0 months in the placebo
arm (HR 0.690).
The rate of CR, a key secondary endpoint in the trial, was 26% in the NINLARO arm versus 14% in the placebo arm.
After a median follow up of 57.8 months in the NINLARO arm versus 58.6
months in the placebo arm for OS, the median OS was not reached in
either arm (HR 0.998).
Median TTP was longer with the NINLARO
combination versus placebo, at 45.8 months in the NINLARO arm versus
26.8 months in the placebo arm (HR 0.738).
Safety data include:
Treatment emergent adverse events (TEAEs) were experienced by 96.6% of
patients receiving NINLARO plus lenalidomide and dexamethasone compared
to 92.6% of patients receiving placebo plus lenalidomide and
dexamethasone.
The most common TEAEs of clinical
importance in the NINLARO arm were diarrhea, rash, peripheral edema,
constipation and nausea.
Grade ≥3 TEAEs were experienced by 88.1% of patients receiving NINLARO versus 81.4% receiving placebo.
The majority of TEAEs were managed without discontinuation, with TEAEs
resulting in 35% regimen discontinuation in the NINLARO arm and 26.9% in
the placebo arm.
The rate of on-study deaths was 7.6% in the NINLARO arm and 6.3% in the placebo arm.
“Insights
from studies like TOURMALINE-MM2 are important, especially to those
patients who may benefit from the convenience of treatment options that
can be taken at home,” said Paul Giusti, President and Chief Executive
Officer, Multiple Myeloma Research Foundation (MMRF). “These critical
learnings enable the community to comprehensively assess the different
treatment combinations available for patients and physicians.”
NINLARO
is currently approved in combination with lenalidomide and
dexamethasone for the treatment of patients with multiple myeloma who
have received at least one prior therapy in more than 65 countries.
NINLARO is not approved as a treatment for newly diagnosed multiple
myeloma.
About the TOURMALINE-MM2 Trial
TOURMALINE-MM2 is
an international, randomized, double-blind, multicenter,
placebo-controlled Phase 3 clinical trial, designed to evaluate NINLARO™
(ixazomib) plus lenalidomide and dexamethasone compared to placebo plus
lenalidomide and dexamethasone, in 705 adult patients with newly
diagnosed multiple myeloma who are not candidates for transplant. The
primary endpoint is progression-free survival (PFS). Key secondary
endpoints include rate of complete response (CR), pain response and
overall survival (OS). For additional information:
https://clinicaltrials.gov/ct2/show/NCT01850524
About Multiple Myeloma
Multiple
myeloma is a life-threatening rare blood cancer that arises from the
plasma cells, a type of white blood cell that is made in the bone
marrow. These plasma cells become abnormal, multiply and release a type
of antibody known as a paraprotein, which causes symptoms of the
disease, including bone pain, frequent or recurring infections and
fatigue, a symptom of anemia. These malignant plasma cells have the
potential to affect many bones in the body and can cause a number of
serious health problems affecting the bones, immune system, kidneys and
red blood cell count. The typical multiple myeloma disease course
includes periods of symptomatic myeloma followed by periods of
remission. Nearly 230,000 people around the world live with multiple
myeloma, with approximately 114,000 new cases diagnosed globally each
year.
About NINLARO™ (ixazomib) capsules
NINLARO™
(ixazomib) is an oral proteasome inhibitor which is being studied across
the continuum of multiple myeloma treatment settings. NINLARO was first
approved by the U.S. Food and Drug Administration (FDA) in November
2015 and is indicated in combination with lenalidomide and dexamethasone
for the treatment of patients with multiple myeloma who have received
at least one prior therapy. NINLARO is currently approved in more than
65 countries, including the United States, Japan and in the European
Union, with nine regulatory filings currently under review. It was the
first oral proteasome inhibitor to enter Phase 3 clinical trials and to
receive approval. In Japan, NINLARO is approved as a maintenance therapy
in multiple myeloma patients who have undergone autologous stem cell
transplant and has been filed for maintenance therapy in patients
ineligible for stem cell transplant.
NINLARO™ (ixazomib): GLOBAL IMPORTANT SAFETY INFORMATION
SPECIAL WARNINGS AND PRECAUTIONS
Thrombocytopenia
has been reported with NINLARO (28% vs. 14% in the NINLARO and placebo
regimens, respectively) with platelet nadirs typically occurring between
Days 14-21 of each 28-day cycle and recovery to baseline by the start
of the next cycle. It did not result in an increase in hemorrhagic
events or platelet transfusions. Monitor platelet counts at least
monthly during treatment with NINLARO and consider more frequent
monitoring during the first three cycles. Manage with dose modifications
and platelet transfusions as per standard medical guidelines.
Gastrointestinal
toxicities have been reported in the NINLARO and placebo regimens
respectively, such as diarrhea (42% vs. 36%), constipation (34% vs.
25%), nausea (26% vs. 21%), and vomiting (22% vs. 11%), occasionally
requiring use of antiemetic and anti-diarrheal medications, and
supportive care.
Peripheral neuropathy was reported with NINLARO
(28% vs. 21% in the NINLARO and placebo regimens, respectively). The
most commonly reported reaction was peripheral sensory neuropathy (19%
and 14% in the NINLARO and placebo regimens, respectively). Peripheral
motor neuropathy was not commonly reported in either regimen (< 1%).
Monitor patients for symptoms of peripheral neuropathy and adjust dosing
as needed.
Peripheral edema was reported with NINLARO (25% vs.
18% in the NINLARO and placebo regimens, respectively). Evaluate
patients for underlying causes and provide supportive care, as
necessary. Adjust the dose of dexamethasone per its prescribing
information or the dose of NINLARO for severe symptoms
Cutaneous
reactions occurred in 19% of patients in the NINLARO regimen compared to
11% of patients in the placebo regimen. The most common type of rash
reported in both regimens was maculo-papular and macular rash. Manage
rash with supportive care, dose modification or discontinuation.
Thrombotic
microangiopathy, sometimes fatal, including thrombotic thrombocytopenic
purpura/hemolytic uremic syndrome (TTP/HUS), have been reported in
patients who received NINLARO. Monitor for signs and symptoms of TPP/HUS
and stop NINLARO if diagnosis is suspected. If the diagnosis of TPP/HUS
is excluded, consider restarting NINLARO. The safety of reinitiating
NINLARO therapy in patients previously experiencing TPP/HUS is not
known.
Hepatotoxicity, drug-induced liver injury, hepatocellular
injury, hepatic steatosis, and hepatitis cholestatic have been
uncommonly reported with NINLARO. Monitor hepatic enzymes regularly and
adjust dose for Grade 3 or 4 symptoms.
Pregnancy- NINLARO can
cause fetal harm. Advise male and female patients of reproductive
potential to use contraceptive measures during treatment and for an
additional 90 days after the final dose of NINLARO. Women of
childbearing potential should avoid becoming pregnant while taking
NINLARO due to potential hazard to the fetus. Women using hormonal
contraceptives should use an additional barrier method of contraception.
Lactation-
It is not known whether NINLARO or its metabolites are excreted in
human milk. There could be potential adverse events in nursing infants
and therefore breastfeeding should be discontinued.
SPECIAL PATIENT POPULATIONS
Hepatic Impairment: Reduce the NINLARO starting dose to 3 mg in patients with moderate or severe hepatic impairment.
Renal
Impairment: Reduce the NINLARO starting dose to 3 mg in patients with
severe renal impairment or end-stage renal disease (ESRD) requiring
dialysis. NINLARO is not dialyzable and, therefore, can be administered
without regard to the timing of dialysis.
DRUG INTERACTIONS
Co-administration of strong CYP3A inducers with NINLARO is not recommended.
ADVERSE REACTIONS
The
most frequently reported adverse reactions (≥ 20%) in the NINLARO
regimen, and greater than in the placebo regimen, were diarrhea (42% vs.
36%), constipation (34% vs. 25%), thrombocytopenia (28% vs. 14%),
peripheral neuropathy (28% vs. 21%), nausea (26% vs. 21%), peripheral
edema (25% vs. 18%), vomiting (22% vs. 11%), and back pain (21% vs.
16%). Serious adverse reactions reported in ≥ 2% of patients included
thrombocytopenia (2%) and diarrhea (2%). For each adverse reaction, one
or more of the three drugs was discontinued in ≤ 1% of patients in the
NINLARO regimen.
For European Union Summary of Product
Characteristics:
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003844/WC500217620.pdf
For US Prescribing Information: https://www.ninlarohcp.com/pdf/prescribing-information.pdf
For Canada Product Monograph: http://www.takedacanada.com/ninlaropm
Takeda’s Commitment to Oncology
Our
core R&D mission is to deliver novel medicines to patients with
cancer worldwide through our commitment to science, breakthrough
innovation and passion for improving the lives of patients. Whether it’s
with our hematology therapies, our robust pipeline, or solid tumor
medicines, we aim to stay both innovative and competitive to bring
patients the treatments they need. For more information, visit
www.takedaoncology.com.
About Takeda Pharmaceutical Company Limited
Takeda
Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) is a global,
values-based, R&D-driven biopharmaceutical leader headquartered in
Japan, committed to bringing Better Health and a Brighter Future to
patients by translating science into highly-innovative medicines. Takeda
focuses its R&D efforts on four therapeutic areas: Oncology, Rare
Diseases, Neuroscience, and Gastroenterology (GI). We also make targeted
R&D investments in Plasma-Derived Therapies and Vaccines. We are
focusing on developing highly innovative medicines that contribute to
making a difference in people's lives by advancing the frontier of new
treatment options and leveraging our enhanced collaborative R&D
engine and capabilities to create a robust, modality-diverse pipeline.
Our employees are committed to improving quality of life for patients
and to working with our partners in health care in approximately 80
countries.
For more information, visit https://www.takeda.com.
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Japanese Media
Kazumi Kobayashi
kazumi.kobayashi@takeda.com
+81 (0) 3-3278-2095
Media outside Japan
Emy Gruppo
emy.gruppo@takeda.com
+1 617-444-2252
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