– First Phase III study to demonstrate a
statistically significant progression-free survival improvement in
first-line metastatic triple negative breast cancer (TNBC) –
– IMpassion130 is the third positive Phase III
study to demonstrate a clinical benefit with the investigational
combination TECENTRIQ® plus ABRAXANE®; studies in triple negative
breast cancer and in non-small cell lung cancer –
Celgene Corporation (NASDAQ:CELG) today announced that the Phase
III IMpassion130 study, which was sponsored by Roche, met its
co-primary endpoint of progression-free survival (PFS). This is the
first phase III study to demonstrate a statistically significant
PFS improvement in first-line metastatic or unresectable locally
advanced triple negative breast cancer (TNBC), a type of breast
cancer with high unmet need.
Results demonstrated that the investigational combination of
TECENTRIQ® (atezolizumab) plus ABRAXANE® (paclitaxel protein-bound
particles for injectable suspension) (albumin-bound) compared to
ABRAXANE® monotherapy, as an initial (first-line) treatment,
significantly reduced the risk of disease worsening or death (PFS)
in patients with metastatic or unresectable locally advanced TNBC
in the intention-to-treat (ITT) and PD-L1 positive populations.
Overall survival is encouraging in the PD-L1 positive population at
this interim analysis, and follow up will continue until the next
planned analysis. Safety in the TECENTRIQ® plus ABRAXANE® arm
appeared consistent with the known safety profiles of the
individual medicines, and no new safety signals were identified
with the combination.
“The IMpassion130 results are extremely encouraging for patients
with this highly aggressive form of breast cancer for which there
are limited options,” said Jay Backstrom, M.D., Chief Medical
Officer for Celgene. “This is the third positive Phase III study to
demonstrate a clinical benefit with TECENTRIQ® plus ABRAXANE® as
part of a treatment regimen; the other studies evaluated this
investigational combination in non-small cell lung cancer patients.
These data demonstrate the potential role of ABRAXANE® as a
preferred chemotherapy partner for immunotherapy combinations.”
Results will be presented at an upcoming medical meeting.
ABRAXANE® is not approved in combination with TECENTRIQ® for any
indication in any geography.
About the IMpassion130 Study
IMpassion130 is a Phase III multicenter, randomized,
double-blind study evaluating the efficacy, safety, and
pharmacokinetics of TECENTRIQ® and ABRAXANE® compared with placebo
in combination with ABRAXANE® in people with locally advanced or
metastatic TNBC who have not received prior systemic therapy for
metastatic breast cancer. The study enrolled 902 people who were
randomized equally (1:1). The co-primary endpoints were
progression-free survival (PFS) per investigator assessment (RECIST
1.1) and overall survival (OS). PFS and OS were assessed in all
randomized participants [intention-to-treat (ITT)] and in those
whose disease expressed the PD-L1 protein. Secondary endpoints
included objective response rate, duration of response and time to
deterioration in Global Health Status/Health-Related Quality of
Life.
During the treatment duration, people in:
- Arm A received TECENTRIQ® at a
fixed dose of 840 milligrams via intravenous (IV) infusion on Days
1 and 15 of each 28-day cycle and ABRAXANE® at a dose of 100
milligrams per square meter via IV infusion on Days 1, 8, and 15 of
each 28-day cycle. ABRAXANE® was administered for a target of at
least 6 cycles, with no maximum. Participants received both agents
until unacceptable toxicity or disease progression.
- Arm B received ABRAXANE® at a
dose of 100 milligrams per square meter via IV infusion on Days 1,
8, and 15 of each 28-day cycle. ABRAXANE® was administered for a
target of at least 6 cycles, with no maximum, and placebo was
administered via IV infusion on Days 1 and 15 of each 28-day cycle.
Participants received both agents until unacceptable toxicity or
disease progression.
About Triple Negative Breast Cancer
Breast cancer is the second most common cancer among women in
the United States. According to the American Cancer Society, it is
estimated that about 266,000 American women will be diagnosed with
invasive breast cancer in 2018, and nearly 41,000 will die from the
disease. Approximately 10-20 percent of breast cancers are triple
negative breast cancer (TNBC). TNBC is an aggressive form of the
disease with a high unmet need. It can be more difficult to treat
because it is not sensitive to hormone therapy or medicines that
target HER2.
TECENTRIQ® is a registered trademark of Genentech, a member of
the Roche Group.
About ABRAXANE®
ABRAXANE is indicated for the treatment of breast cancer
after failure of combination chemotherapy for metastatic disease or
relapse within 6 months of adjuvant chemotherapy. Prior therapy
should have included an anthracycline unless clinically
contraindicated.
ABRAXANE is indicated for the first-line treatment of locally
advanced or metastatic non–small cell lung cancer, in combination
with carboplatin, in patients who are not candidates for curative
surgery or radiation therapy.
Important Safety Information for ABRAXANE®
WARNING -
NEUTROPENIA
- Do not administer ABRAXANE therapy
to patients who have baseline neutrophil counts of less than 1500
cells/mm3. In order to monitor the occurrence of bone
marrow suppression, primarily neutropenia, which may be severe and
result in infection, it is recommended that frequent peripheral
blood cell counts be performed on all patients receiving
ABRAXANE
- Note: An albumin form of paclitaxel
may substantially affect a drug’s functional properties relative to
those of drug in solution. DO NOT SUBSTITUTE FOR OR WITH OTHER
PACLITAXEL FORMULATIONS
CONTRAINDICATIONS
Neutrophil Counts
- ABRAXANE should not be used in patients
who have baseline neutrophil counts of <1500 cells/mm3
Hypersensitivity
- Patients who experience a severe
hypersensitivity reaction to ABRAXANE should not be rechallenged
with the drug
WARNINGS AND PRECAUTIONS
Hematologic Effects
- Bone marrow suppression (primarily
neutropenia) is dose-dependent and a dose-limiting toxicity of
ABRAXANE. In clinical studies, Grade 3-4 neutropenia occurred in
34% of patients with metastatic breast cancer (MBC) and 47% of
patients with non–small cell lung cancer (NSCLC)
- Monitor for myelotoxicity by performing
complete blood cell counts frequently, including prior to dosing on
Day 1 (for MBC) and Days 1, 8, and 15 for NSCLC
- Do not administer ABRAXANE to patients
with baseline absolute neutrophil counts (ANC) of less than 1500
cells/mm3
- In the case of severe neutropenia
(<500 cells/mm3 for 7 days or more) during a course of ABRAXANE
therapy, reduce the dose of ABRAXANE in subsequent courses in
patients with either MBC or NSCLC
- In patients with MBC, resume treatment
with every-3-week cycles of ABRAXANE after ANC recovers to a level
>1500 cells/mm3 and platelets recover to a level
>100,000 cells/mm3
- In patients with NSCLC, resume
treatment if recommended at permanently reduced doses for both
weekly ABRAXANE and every-3-week carboplatin after ANC recovers to
at least 1500 cells/mm3 and platelet count of at least 100,000
cells/mm3 on Day 1 or to an ANC of at least 500 cells/mm3 and
platelet count of at least 50,000 cells/mm3 on Days 8 or 15 of the
cycle
Nervous System
- Sensory neuropathy is dose- and
schedule-dependent
- The occurrence of Grade 1 or 2 sensory
neuropathy does not generally require dose modification
- If ≥ Grade 3 sensory neuropathy
develops, withhold ABRAXANE treatment until resolution to Grade 1
or 2 for MBC or until resolution to ≤ Grade 1 for NSCLC
followed by a dose reduction for all subsequent courses of
ABRAXANE
Hypersensitivity
- Severe and sometimes fatal
hypersensitivity reactions, including anaphylactic reactions, have
been reported
- Patients who experience a severe
hypersensitivity reaction to ABRAXANE should not be rechallenged
with this drug
Hepatic Impairment
- Because the exposure and toxicity of
paclitaxel can be increased with hepatic impairment, administration
of ABRAXANE in patients with hepatic impairment should be performed
with caution
- Patients with hepatic impairment may be
at an increased risk of toxicity, particularly from
myelosuppression, and should be monitored for development of
profound myelosuppression
- For MBC and NSCLC, the starting dose
should be reduced for patients with moderate or severe hepatic
impairment
Albumin (Human)
- ABRAXANE contains albumin (human), a
derivative of human blood
Use in Pregnancy: Pregnancy Category D
- ABRAXANE can cause fetal harm when
administered to a pregnant woman
- If this drug is used during pregnancy,
or if the patient becomes pregnant while receiving this drug, the
patient should be apprised of the potential hazard to the
fetus
- Women of childbearing potential should
be advised to avoid becoming pregnant while receiving ABRAXANE
Use in Men
- Men should be advised not to father a
child while receiving ABRAXANE
ADVERSE REACTIONS
Randomized Metastatic Breast Cancer (MBC) Study
- The most common adverse reactions
(≥20%) with single-agent use of ABRAXANE vs paclitaxel injection in
the MBC study are alopecia (90%, 94%), neutropenia (all cases 80%,
82%; severe 9%, 22%), sensory neuropathy (any symptoms 71%, 56%;
severe 10%, 2%), abnormal ECG (all patients 60%, 52%; patients with
normal baseline 35%, 30%), fatigue/asthenia (any 47%, 39%; severe
8%, 3%), myalgia/arthralgia (any 44%, 49%; severe 8%, 4%), AST
elevation (any 39%, 32%), alkaline phosphatase elevation (any 36%,
31%), anemia (any 33%, 25%; severe 1%, <1%), nausea (any 30%,
22%; severe 3%, <1%), diarrhea (any 27%, 15%; severe <1%, 1%)
and infections (24%, 20%), respectively
- Sensory neuropathy was the cause of
ABRAXANE discontinuation in 7/229 (3%) patients
- Other adverse reactions of note with
the use of ABRAXANE vs paclitaxel injection included vomiting (any
18%, 10%; severe 4%, 1%), fluid retention (any 10%, 8%; severe 0%,
<1%), mucositis (any 7%, 6%; severe <1%, 0%), hepatic
dysfunction (elevations in bilirubin 7%, 7%), hypersensitivity
reactions (any 4%, 12%; severe 0%, 2%), thrombocytopenia (any 2%,
3%; severe <1%, <1%), neutropenic sepsis (<1%, <1%),
and injection site reactions (<1%, 1%), respectively.
Dehydration and pyrexia were also reported
- Renal dysfunction (any 11%, severe 1%)
was reported in patients treated with ABRAXANE (n=229)
- In all ABRAXANE-treated patients
(n=366), ocular/visual disturbances were reported (any 13%; severe
1%)
- Severe cardiovascular events possibly
related to single-agent ABRAXANE occurred in approximately 3% of
patients and included cardiac ischemia/infarction, chest pain,
cardiac arrest, supraventricular tachycardia, edema, thrombosis,
pulmonary thromboembolism, pulmonary emboli, and hypertension
- Cases of cerebrovascular attacks
(strokes) and transient ischemic attacks have been reported
Non–Small Cell Lung Cancer (NSCLC) Study
- The most common adverse reactions
(≥20%) of ABRAXANE in combination with carboplatin are anemia,
neutropenia, thrombocytopenia, alopecia, peripheral neuropathy,
nausea, and fatigue
- The most common serious adverse
reactions of ABRAXANE in combination with carboplatin for NSCLC are
anemia (4%) and pneumonia (3%)
- The most common adverse reactions
resulting in permanent discontinuation of ABRAXANE are neutropenia
(3%), thrombocytopenia (3%), and peripheral neuropathy (1%)
- The most common adverse reactions
resulting in dose reduction of ABRAXANE are neutropenia (24%),
thrombocytopenia (13%), and anemia (6%)
- The most common adverse reactions
leading to withholding or delay in ABRAXANE dosing are neutropenia
(41%), thrombocytopenia (30%), and anemia (16%)
- The following common (≥10% incidence)
adverse reactions were observed at a similar incidence in ABRAXANE
plus carboplatin–treated and paclitaxel injection plus
carboplatin–treated patients: alopecia (56%), nausea (27%), fatigue
(25%), decreased appetite (17%), asthenia (16%), constipation
(16%), diarrhea (15%), vomiting (12%), dyspnea (12%), and rash
(10%); incidence rates are for the ABRAXANE plus carboplatin
treatment group
- Adverse reactions with a difference of
≥2%, Grade 3 or higher, with combination use of ABRAXANE and
carboplatin vs combination use of paclitaxel injection and
carboplatin in NSCLC are anemia (28%, 7%), neutropenia (47%, 58%),
thrombocytopenia (18%, 9%), and peripheral neuropathy (3%, 12%),
respectively
- Adverse reactions with a difference of
≥5%, Grades 1-4, with combination use of ABRAXANE and carboplatin
vs combination use of paclitaxel injection and carboplatin in NSCLC
are anemia (98%, 91%), thrombocytopenia (68%, 55%), peripheral
neuropathy (48%, 64%), edema peripheral (10%, 4%), epistaxis (7%,
2%), arthralgia (13%, 25%), and myalgia (10%, 19%),
respectively
- Neutropenia (all grades) was reported
in 85% of patients who received ABRAXANE and carboplatin vs 83% of
patients who received paclitaxel injection and carboplatin
Postmarketing Experience With ABRAXANE and Other Paclitaxel
Formulations
- Severe and sometimes fatal
hypersensitivity reactions have been reported with ABRAXANE. The
use of ABRAXANE in patients previously exhibiting hypersensitivity
to paclitaxel injection or human albumin has not been studied
- There have been reports of congestive
heart failure, left ventricular dysfunction, and atrioventricular
block with ABRAXANE, primarily among individuals with underlying
cardiac history or prior exposure to cardiotoxic drugs
- There have been reports of
extravasation of ABRAXANE. Given the possibility of extravasation,
it is advisable to monitor closely the ABRAXANE infusion site for
possible infiltration during drug administration
DRUG INTERACTIONS
- Caution should be exercised when
administering ABRAXANE concomitantly with medicines known to
inhibit or induce either CYP2C8 or CYP3A4
USE IN SPECIFIC POPULATIONS
Nursing Mothers
- It is not known whether paclitaxel is
excreted in human milk. Because many drugs are excreted in human
milk and because of the potential for serious adverse reactions in
nursing infants, a decision should be made to discontinue nursing
or to discontinue the drug, taking into account the importance of
the drug to the mother
Pediatric
- The safety and effectiveness of
ABRAXANE in pediatric patients have not been evaluated
Geriatric
- A higher incidence of epistaxis,
diarrhea, dehydration, fatigue, and peripheral edema was found in
patients 65 years or older who received ABRAXANE for MBC in a
pooled analysis of clinical studies
- Myelosuppression, peripheral
neuropathy, and arthralgia were more frequent in patients
≥65 years of age treated with ABRAXANE and carboplatin in
NSCLC
Renal Impairment
- There are insufficient data to permit
dosage recommendations in patients with severe renal impairment or
end stage renal disease (estimated creatinine clearance <30
mL/min)
DOSAGE AND ADMINISTRATION
- Do not administer ABRAXANE to any
patient with total bilirubin greater than 5 x ULN or AST greater
than 10 x ULN
- For MBC and NSCLC, reduce starting dose
in patients with moderate to severe hepatic impairment
- Dose reductions or discontinuation may
be needed based on severe hematologic or neurologic toxicity
- Monitor patients closely
Please see full Prescribing Information, including
Boxed WARNING.
About Celgene
Celgene Corporation, headquartered in Summit, New
Jersey, is an integrated global biopharmaceutical company engaged
primarily in the discovery, development and commercialization of
innovative therapies for the treatment of cancer and inflammatory
diseases through next-generation solutions in protein homeostasis,
immuno-oncology, epigenetics, immunology and neuro-inflammation.
For more information, please visit www.celgene.com.
Follow Celgene on Social
Media: @Celgene, Pinterest, LinkedIn, Facebook and YouTube.
Forward-Looking Statements
This press release contains forward-looking statements, which
are generally statements that are not historical facts.
Forward-looking statements can be identified by the words
"expects," "anticipates," "believes," "intends," "estimates,"
"plans," "will," “outlook” and similar expressions. Forward-looking
statements are based on management’s current plans, estimates,
assumptions and projections, and speak only as of the date they are
made. We undertake no obligation to update any forward-looking
statement in light of new information or future events, except as
otherwise required by law. Forward-looking statements involve
inherent risks and uncertainties, most of which are difficult to
predict and are generally beyond our control. Actual results or
outcomes may differ materially from those implied by the
forward-looking statements as a result of the impact of a number of
factors, many of which are discussed in more detail in our Annual
Report on Form 10-K and our other reports filed with the Securities
and Exchange Commission.
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