Combinations of KEYTRUDA® (pembrolizumab) with
Alimta® (pemetrexed), Cyramza® (ramucirumab), or necitumumab to be
explored
Merck (NYSE:MRK), known as MSD outside the US and Canada, and
Eli Lilly and Company (NYSE:LLY) announced today an oncology
clinical trial collaboration to evaluate the safety, tolerability
and efficacy of KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1
therapy, in combination with Lilly compounds in multiple clinical
trials:
- Merck will conduct a Phase 2 study
examining the combination of pembrolizumab with pemetrexed in
first-line non-squamous, non-small cell lung cancer (NSCLC). This
study is currently enrolling.
- Lilly will conduct a multiple-arm Phase
1/2 study examining the combination of ramucirumab with
pembrolizumab in multiple tumors. This study is anticipated to
begin in 2015.
- Lilly will conduct a Phase 1/2 study
examining the combination of necitumumab with pembrolizumab in
NSCLC. This study is anticipated to begin in 2015.
The agreement is between Lilly and Merck, through a subsidiary.
Additional details of the collaboration were not disclosed.
“Cancer is not one disease but rather more than 200 diseases,
all of which have different causes and treatments,” said Richard
Gaynor, M.D., senior vice president, product development and
medical affairs, Lilly Oncology. “Therefore research into
combinations of immune-based therapies with other agents that could
address these different tumor types is important. This
collaboration between Lilly and Merck represents each company’s
strong commitment to patients fighting these devastating
diseases.”
“Our understanding of the immune system’s role and its impact in
the treatment of cancer continues to grow,” said Eric Rubin, M.D.,
vice president, global clinical development, oncology, Merck
Research Laboratories. “Collaborations such as this one are
important in advancing the investigation of novel immuno-oncology
combinations in different cancers, and to achieving our shared goal
of bringing meaningful benefits to patients facing cancer."
About KEYTRUDA® (pembrolizumab)
KEYTRUDA (pembrolizumab) is a humanized monoclonal antibody that
blocks the interaction between PD-1 and its ligands, PD-L1 and
PD-L2. By binding to the PD-1 receptor and blocking the interaction
with the receptor ligands, KEYTRUDA releases the PD-1
pathway-mediated inhibition of the immune response, including the
anti-tumor immune response.
KEYTRUDA is indicated in the United States at a dose of 2 mg/kg
every three weeks for the treatment of patients with unresectable
or metastatic melanoma and disease progression following ipilimumab
and, if BRAF V600 mutation positive, a BRAF inhibitor. This
indication is approved under accelerated approval based on tumor
response rate and durability of response. An improvement in
survival or disease-related symptoms has not yet been established.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in the
confirmatory trials.
About ALIMTA® (pemetrexed)
In 2004, ALIMTA received consecutive approvals: it was the first
agent to be approved in combination with cisplatin as a treatment
for patients with malignant pleural mesothelioma, whose disease is
unresectable or who are otherwise not candidates for curative
surgery, and then as a single agent for the second-line treatment
of patients with locally advanced or metastatic NSCLC after prior
chemotherapy treatment.
In 2008, ALIMTA, in combination with cisplatin, was approved as
a first-line treatment for locally advanced or metastatic NSCLC for
patients with nonsquamous histology. At the time of the first-line
approval, the FDA also approved a change to the second-line
indication. ALIMTA is now indicated as a single agent for the
treatment of patients with locally advanced or metastatic,
nonsquamous NSCLC after prior chemotherapy.
In 2009, ALIMTA was approved as a maintenance therapy for
locally advanced or metastatic NSCLC, specifically for patients
with a nonsquamous histology whose disease has not progressed after
four cycles of platinum-based first-line chemotherapy.
In 2012, ALIMTA was approved by the FDA as a continuation
maintenance therapy for locally-advanced or metastatic NSCLC,
following first-line therapy with ALIMTA plus cisplatin in patients
with a nonsquamous histology.
ALIMTA is not indicated for treatment of patients with squamous
cell NSCLC. Myelosuppression is usually the dose-limiting toxicity
with ALIMTA therapy.
About CYRAMZA® (ramucirumab)
CYRAMZA as a single agent, or in combination with paclitaxel (a
type of chemotherapy), is approved for the treatment of people with
advanced or metastatic gastric or gastroesophageal junction (GEJ)
adenocarcinoma whose cancer has progressed on or after prior
fluoropyrimidine- or platinum-containing chemotherapy.
CYRAMZA is an antiangiogenic therapy. It is a vascular
endothelial growth factor (VEGF) Receptor 2 antagonist that
specifically binds and blocks activation of VEGF Receptor 2, by
blocking the binding of VEGF receptor ligands VEGF-A, VEGF-C, and
VEGF-D. CYRAMZA inhibited angiogenesis in an in
vivo animal model.
About Necitumumab
Necitumumab is an investigational recombinant human IgG1
monoclonal antibody that is designed to block the ligand binding
site of the human epidermal growth factor receptor 1 (EGFR).
Activation of EGFR has been correlated with malignant progression,
induction of angiogenesis and inhibition of apoptosis or cell
death.
Selected Important Safety Information for KEYTRUDA
Pneumonitis occurred in 12 (2.9%) of 411 patients with advanced
melanoma receiving KEYTRUDA (the approved indication in the United
States), including Grade 2 or 3 cases in 8 (1.9%) and 1 (0.2%)
patients, respectively. Monitor patients for signs and symptoms of
pneumonitis. Evaluate suspected pneumonitis with radiographic
imaging. Administer corticosteroids for Grade 2 or greater
pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue
KEYTRUDA for Grade 3 or 4 pneumonitis.
Colitis (including microscopic colitis) occurred in 4 (1%) of
411 patients, including Grade 2 or 3 cases in 1 (0.2%) and 2 (0.5%)
patients respectively, receiving KEYTRUDA. Monitor patients for
signs and symptoms of colitis. Administer corticosteroids for Grade
2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3;
permanently discontinue KEYTRUDA for Grade 4 colitis.
Hepatitis (including autoimmune hepatitis) occurred in 2 (0.5%)
of 411 patients, including a Grade 4 case in 1 (0.2%) patient,
receiving KEYTRUDA. Monitor patients for changes in liver function.
Administer corticosteroids for Grade 2 or greater hepatitis and,
based on severity of liver enzyme elevations, withhold or
discontinue KEYTRUDA.
Hypophysitis occurred in 2 (0.5%) of 411 patients, including a
Grade 2 case in 1 and a Grade 4 case in 1 (0.2% each) patient,
receiving KEYTRUDA. Monitor for signs and symptoms of hypophysitis.
Administer corticosteroids for Grade 2 or greater hypophysitis.
Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3;
and permanently discontinue KEYTRUDA for Grade 4 hypophysitis.
Nephritis occurred in 3 (0.7%) patients receiving KEYTRUDA,
consisting of one case of Grade 2 autoimmune nephritis (0.2%) and
two cases of interstitial nephritis with renal failure (0.5%), one
Grade 3 and one Grade 4. Monitor patients for changes in renal
function. Administer corticosteroids for Grade 2 or greater
nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue
KEYTRUDA for Grade 3 or 4 nephritis.
Hyperthyroidism occurred in 5 (1.2%) of 411 patients, including
Grade 2 or 3 cases in 2 (0.5%) and 1 (0.2%) patients respectively,
receiving KEYTRUDA. Hypothyroidism occurred in 34 (8.3%) of 411
patients, including a Grade 3 case in 1 (0.2%) patient, receiving
KEYTRUDA. Thyroid disorders can occur at any time during treatment.
Monitor patients for changes in thyroid function (at the start of
treatment, periodically during treatment, and as indicated based on
clinical evaluation) and for clinical signs and symptoms of thyroid
disorders. Administer corticosteroids for Grade 3 or greater
hyperthyroidism. Withhold KEYTRUDA for Grade 3; permanently
discontinue KEYTRUDA for Grade 4 hyperthyroidism. Isolated
hypothyroidism may be managed with replacement therapy without
treatment interruption and without corticosteroids.
Other clinically important immune-mediated adverse reactions can
occur. The following clinically significant, immune-mediated
adverse reactions occurred in less than 1% of patients treated with
KEYTRUDA: exfoliative dermatitis, uveitis, arthritis, myositis,
pancreatitis, hemolytic anemia, partial seizures arising in a
patient with inflammatory foci in brain parenchyma, adrenal
insufficiency, myasthenic syndrome, optic neuritis, and
rhabdomyolysis.
For suspected immune-mediated adverse reactions, ensure adequate
evaluation to confirm etiology or exclude other causes. Based on
the severity of the adverse reaction, withhold KEYTRUDA and
administer corticosteroids. Upon improvement of the adverse
reaction to Grade 1 or less, initiate corticosteroid taper and
continue to taper over at least 1 month. Restart KEYTRUDA if the
adverse reaction remains at Grade 1 or less. Permanently
discontinue KEYTRUDA for any severe or Grade 3 immune-mediated
adverse reaction that recurs and for any life-threatening
immune-mediated adverse reaction.
Based on its mechanism of action, KEYTRUDA may cause fetal harm
when administered to a pregnant woman. If used during pregnancy, or
if the patient becomes pregnant during treatment, apprise the
patient of the potential hazard to a fetus. Advise females of
reproductive potential to use highly effective contraception during
treatment and for 4 months after the last dose of KEYTRUDA.
For the treatment of advanced melanoma, KEYTRUDA was
discontinued for adverse reactions in 6% of 89 patients who
received the recommended dose of 2 mg/kg and 9% of 411 patients
across all doses studied. Serious adverse reactions occurred in 36%
of patients receiving KEYTRUDA. The most frequent serious adverse
drug reactions reported in 2% or more of patients were renal
failure, dyspnea, pneumonia, and cellulitis.
The most common adverse reactions (reported in ≥20% of patients)
were fatigue (47%), cough (30%), nausea (30%), pruritus (30%), rash
(29%), decreased appetite (26%), constipation (21%), arthralgia
(20%), and diarrhea (20%).
The recommended dose of KEYTRUDA is 2 mg/kg administered as an
intravenous infusion over 30 minutes every three weeks until
disease progression or unacceptable toxicity. No formal
pharmacokinetic drug interaction studies have been conducted with
KEYTRUDA. It is not known whether KEYTRUDA is excreted in human
milk. Because many drugs are excreted in human milk, instruct women
to discontinue nursing during treatment with KEYTRUDA. Safety and
effectiveness of KEYTRUDA have not been established in pediatric
patients.
Important Safety Information for ALIMTA® (pemetrexed for
injection)
Myelosuppression is usually the dose-limiting toxicity with
ALIMTA therapy.
Contraindication
ALIMTA is contraindicated in patients who have a history of
severe hypersensitivity reaction to pemetrexed.
Warnings and Precautions
Prior to treatment with ALIMTA, patients must be instructed to
initiate supplementation with oral folic acid. Additionally,
intramuscular injections of vitamin B12 are also required prior to
ALIMTA treatment. Folic acid and vitamin B12 supplementation should
be continued throughout treatment as they may reduce the severity
of treatment-related hematologic and GI toxicities. Dexamethasone
or its equivalent should be administered the day before, the day
of, and the day after ALIMTA treatment.
ALIMTA can suppress bone marrow function, as manifested by
neutropenia, thrombocytopenia, and anemia (or pancytopenia). Reduce
doses for subsequent cycles based on hematologic and nonhematologic
toxicities.
ALIMTA should not be administered to patients with a creatinine
clearance <45 mL/min. One patient with severe renal impairment
(creatinine clearance 19 mL/min) who did not receive folic acid and
vitamin B12 died of drug-related toxicity following administration
of ALIMTA alone.
Caution should be used when administering NSAIDs concurrently
with ALIMTA to patients with mild to moderate renal insufficiency
(creatinine clearance from 45 to 79 mL/min). Patients with mild to
moderate renal insufficiency should avoid taking NSAIDs with short
elimination half-lives for a period of 2 days before, the day of,
and 2 days following administration of ALIMTA. In the absence of
data regarding potential interaction between ALIMTA and NSAIDs with
longer half-lives, all patients taking these NSAIDs should
interrupt dosing for at least 5 days before, the day of, and 2 days
following ALIMTA administration. If concomitant administration of
NSAIDs is necessary, patients should be monitored closely for
toxicity, especially myelosuppression, renal, and gastrointestinal
toxicity. No dose adjustment of ALIMTA is needed with concomitant
NSAIDs in patients with normal renal function.
Do not initiate a cycle of treatment in patients unless the ANC
is ≥1500 cells/mm3, the platelet count is ≥100,000 cells/mm3, and
creatinine clearance is ≥45 mL/min.
Pregnancy Category D—ALIMTA may cause fetal harm when
administered to a pregnant woman. Women should be apprised of the
potential hazard to the fetus and should be advised to use
effective contraceptive measures to prevent pregnancy during
treatment with ALIMTA.
Drug Interactions
See Warnings and Precautions for specific information regarding
NSAID administration in patients with renal insufficiency.
Concomitant administration of nephrotoxic drugs or substances
that are tubularly secreted could result in delayed clearance of
ALIMTA.
Use in Specific Patient Populations
It is recommended that nursing be discontinued if the mother is
being treated with ALIMTA or discontinue the drug, taking into
account the importance of the drug for the mother.
Efficacy of ALIMTA in pediatric patients has not been
demonstrated. The most common toxicities reported in the studied
pediatric patients were hematological (leukopenia,
neutropenia/granulocytopenia, anemia, thrombocytopenia, and
lymphopenia), liver function abnormalities (increased ALT/AST),
fatigue, and nausea.
Dosage and Administration Guidelines
Complete blood cell counts, including platelet counts and
periodic chemistry tests, which include renal and hepatic function
tests, should be performed on all patients receiving ALIMTA.
Dose adjustments at the start of a subsequent cycle should be
based on nadir hematologic counts or maximum nonhematologic
toxicity from the preceding cycle of therapy. Modify or suspend
therapy according to the Dosage Reduction Guidelines in the full
Prescribing Information.
Abbreviated Adverse Reactions (% incidence) – 1st-line
advanced nonsquamous non-small cell lung cancer (NS NSCLC)
The most severe adverse reactions (grades 3-4) with ALIMTA in
combination with cisplatin versus gemcitabine in combination with
cisplatin, respectively, for the 1st-line treatment of patients
with advanced nonsquamous non-small cell lung cancer (NSCLC) were
neutropenia (15% vs 27%); leukopenia (5% vs 8%); thrombocytopenia
(4% vs 13%); anemia (6% vs 10%); fatigue (7% vs 5%); nausea (7% vs
4%); vomiting (6% vs 6%); anorexia (2% vs 1%); creatinine elevation
(1% vs 1%); and diarrhea (1% vs 2%).
Common adverse reactions (all grades) with ALIMTA in combination
with cisplatin versus gemcitabine in combination with cisplatin,
respectively, were nausea (56% vs 53%); fatigue (43% vs 45%);
vomiting (40% vs 36%); anemia (33% vs 46%); neutropenia (29% vs
38%); anorexia (27% vs 24%); constipation (21% vs 20%); leukopenia
(18% vs 21%); stomatitis/pharyngitis (14% vs 12%); alopecia (12% vs
21%); diarrhea (12% vs 13%); thrombocytopenia (10% vs 27%);
neuropathy/sensory (9% vs 12%); taste disturbance (8% vs 9%);
rash/desquamation (7% vs 8%); dyspepsia/heartburn (5% vs 6%); and
creatinine elevation (10% vs 7%).
Abbreviated Adverse Reactions (% incidence) – Maintenance in
advanced NS NSCLC following non-ALIMTA containing, platinum-based
induction therapy
The most severe adverse reactions (grades 3-4) with ALIMTA as a
single agent versus placebo, respectively, for the maintenance
treatment of patients with locally advanced nonsquamous non-small
cell lung cancer (NS NSCLC) following non-ALIMTA containing
platinum-based induction therapy were anemia (3% vs 1%);
neutropenia (3% vs 0%); leukopenia (2% vs 1%); fatigue (5% vs 1%);
nausea (1% vs 1%); anorexia (2% vs 0%); mucositis/stomatitis (1% vs
0%); diarrhea (1% vs 0%); infection (2% vs 0%); and
neuropathy-sensory (1% vs 0%).
Common adverse reactions (all grades) with ALIMTA as a single
agent versus placebo, respectively, after non-ALIMTA containing
platinum-based induction therapy were anemia (15% vs 6%);
neutropenia (6% vs 0%); leukopenia (6% vs 1%); increased ALT (10%
vs 4%); increased AST (8% vs 4%); fatigue (25% vs 11%); nausea (19%
vs 6%); anorexia (19% vs 5%); vomiting (9% vs 1%);
mucositis/stomatitis (7% vs 2%); diarrhea (5% vs 3%); infection (5%
vs 2%); neuropathy-sensory (9% vs 4%); and rash/desquamation (10%
vs 3%).
Abbreviated Adverse Reactions (% incidence) – Maintenance in
advanced NS NSCLC following ALIMTA plus cisplatin induction
therapy
The most severe adverse reactions (grades 3-4) with ALIMTA as a
single agent versus placebo, respectively, for the maintenance
treatment of patients with locally advanced nonsquamous non-small
cell lung cancer (NS NSCLC) following ALIMTA plus cisplatin
induction therapy were anemia (4.8% vs 0.6%); neutropenia (3.9% vs
0%); and fatigue (4.5% vs 0.6%).
Common adverse reactions (all grades) with ALIMTA as a single
agent versus placebo, respectively, following ALIMTA plus cisplatin
induction therapy were anemia (15% vs 4.8%); neutropenia (9% vs
0.6%); fatigue (18% vs 11%); nausea (12% vs 2.4%); vomiting (6% vs
1.8%); mucositis/stomatitis (5% vs 2.4%); and edema (5% vs
3.6%).
Abbreviated Adverse Reactions (% incidence) – 2nd-line
advanced NS NSCLC
The most severe adverse reactions (grades 3-4) with ALIMTA as a
single agent versus docetaxel, respectively, for the 2nd-line
treatment of patients with advanced non-small cell lung cancer
(NSCLC) were neutropenia (5% vs 40%); leukopenia (4% vs 27%);
thrombocytopenia (2% vs 0%); anemia (4% vs 4%); fatigue (5% vs 5%);
nausea (3% vs 2%); anorexia (2% vs 3%); vomiting (2% vs 1%);
increased ALT (2% vs 0%); increased AST (1% vs 0%); and
stomatitis/pharyngitis (1% vs 1%).
Common adverse reactions (all grades) with ALIMTA as a single
agent versus docetaxel, respectively, were fatigue (34% vs 36%);
nausea (31% vs 17%); anorexia (22% vs 24%); anemia (19% vs 22%);
vomiting (16% vs 12%); stomatitis/pharyngitis (15% vs 17%); rash
(14% vs 6%); diarrhea (13% vs 24%); leukopenia (12% vs 34%);
thrombocytopenia (8% vs 1%); increased ALT (8% vs 1%); increased
AST (7% vs 1%); constipation (6% vs 4%); fever (8% vs 8%); pruritus
(7% vs 2%); alopecia (6% vs 38%); and neutropenia (11% vs 45%).
For safety and dosing guidelines, see complete Warnings and
Precautions, Adverse Reactions, and Dosage and Administration
sections in the accompanying full Prescribing Information.
PM_HCP_ISI_NSCLCall_17OCT2012
IMPORTANT SAFETY INFORMATION FOR CYRAMZA
WARNING: HEMORRHAGECYRAMZA increased the risk of
hemorrhage, including severe and sometimes fatal hemorrhagic
events. Permanently discontinue CYRAMZA in patients who experience
severe bleeding.
Warnings and Precautions
Hemorrhage
- CYRAMZA increased the risk of
hemorrhage and gastrointestinal hemorrhage including severe and
sometimes fatal hemorrhagic events. In Study 1, which evaluated
CYRAMZA as a single agent in advanced gastric cancer, the incidence
of severe bleeding was 3.4% for CYRAMZA and 2.6% for placebo. In
Study 2, which evaluated CYRAMZA plus paclitaxel in advanced
gastric cancer, the incidence of severe bleeding was 4.3% for
CYRAMZA plus paclitaxel and 2.4% for placebo plus paclitaxel.
Patients with gastric cancer receiving nonsteroidal
anti-inflammatory drugs (NSAIDs) were excluded from enrollment in
Studies 1 and 2; therefore, the risk of gastric hemorrhage in
CYRAMZA-treated patients with gastric tumors receiving NSAIDs is
unknown. In Study 3, which evaluated CYRAMZA plus docetaxel in
metastatic non-small cell lung cancer (NSCLC), the incidence of
severe bleeding was 2.4% for CYRAMZA plus docetaxel and 2.3% for
placebo plus docetaxel. Patients with NSCLC receiving therapeutic
anticoagulation or chronic therapy with NSAIDs or other
antiplatelet therapy other than once-daily aspirin or with
radiographic evidence of major airway or blood vessel invasion or
intratumor cavitation were excluded from Study 3; therefore, the
risk of pulmonary hemorrhage in these groups of patients is
unknown. Permanently discontinue CYRAMZA in patients who experience
severe bleeding.
Arterial Thromboembolic Events
- Serious, sometimes fatal, arterial
thromboembolic events (ATEs) including myocardial infarction,
cardiac arrest, cerebrovascular accident, and cerebral ischemia
occurred in clinical trials including 1.7% of 236 patients who
received CYRAMZA as a single agent for gastric cancer in Study 1.
Permanently discontinue CYRAMZA in patients who experience a severe
ATE.
Hypertension
- An increased incidence of severe
hypertension occurred in patients receiving CYRAMZA as a single
agent (8%) as compared to placebo (3%), in patients receiving
CYRAMZA plus paclitaxel (15%) as compared to placebo plus
paclitaxel (3%), and in patients receiving CYRAMZA plus docetaxel
(6%) as compared to placebo plus docetaxel (2%). Control
hypertension prior to initiating treatment with CYRAMZA. Monitor
blood pressure every 2 weeks or more frequently as indicated during
treatment. Temporarily suspend CYRAMZA for severe hypertension
until medically controlled. Permanently discontinue CYRAMZA if
medically significant hypertension cannot be controlled with
antihypertensive therapy or in patients with hypertensive crisis or
hypertensive encephalopathy.
Infusion-Related Reactions
- Prior to the institution of
premedication recommendations across clinical trials of CYRAMZA,
infusion-related reactions (IRRs) occurred in 6 out of 37 patients
(16%), including 2 severe events. The majority of IRRs across
trials occurred during or following a first or second CYRAMZA
infusion. Symptoms of IRRs included rigors/tremors, back
pain/spasms, chest pain and/or tightness, chills, flushing,
dyspnea, wheezing, hypoxia, and paresthesia. In severe cases,
symptoms included bronchospasm, supraventricular tachycardia, and
hypotension. Monitor patients during the infusion for signs and
symptoms of IRRs in a setting with available resuscitation
equipment. Immediately and permanently discontinue CYRAMZA for
Grade 3 or 4 IRRs.
Gastrointestinal Perforations
- CYRAMZA is an antiangiogenic therapy
that can increase the risk of gastrointestinal perforation, a
potentially fatal event. Four of 570 patients (0.7%) who received
CYRAMZA as a single agent in advanced gastric cancer clinical
trials experienced gastrointestinal perforation. In Study 2, the
incidence of gastrointestinal perforation was 1.2% for CYRAMZA plus
paclitaxel as compared to 0.3% for placebo plus paclitaxel. In
Study 3, the incidence of gastrointestinal perforation was 1% for
CYRAMZA plus docetaxel as compared to 0.3% for placebo plus
docetaxel. Permanently discontinue CYRAMZA in patients who
experience a gastrointestinal perforation.
Impaired Wound Healing
- CYRAMZA has not been studied in
patients with serious or nonhealing wounds. CYRAMZA is an
antiangiogenic therapy with the potential to adversely affect wound
healing. Withhold CYRAMZA prior to surgery. Resume CYRAMZA
following the surgical intervention based on clinical judgment of
adequate wound healing. If a patient develops wound healing
complications during therapy, discontinue CYRAMZA until the wound
is fully healed.
Clinical Deterioration in Child-Pugh B or C Cirrhosis
- Clinical deterioration, manifested by
new onset or worsening encephalopathy, ascites, or hepatorenal
syndrome, was reported in patients with Child-Pugh B or C cirrhosis
who received single-agent CYRAMZA. Use CYRAMZA in patients with
Child-Pugh B or C cirrhosis only if the potential benefits of
treatment are judged to outweigh the risks of clinical
deterioration.
Reversible Posterior Leukoencephalopathy Syndrome
(RPLS)
- RPLS has been reported at a rate of
<0.1% in clinical studies with CYRAMZA. Confirm the diagnosis of
RPLS with MRI and discontinue CYRAMZA in patients who develop RPLS.
Symptoms may resolve or improve within days, although some patients
with RPLS can experience ongoing neurologic sequelae or death.
Most Common Adverse Reactions—Single Agent
- The most commonly reported adverse
reactions (all grades; Grade 3/4) occurring in ≥5% of patients
receiving CYRAMZA and ≥2% higher than placebo in Study 1 were
hypertension (16% vs 8%; 8% vs 3%), diarrhea (14% vs 9%; 1% vs 2%),
headache (9% vs 3%; 0% vs 0%), and hyponatremia (6% vs 2%; 3% vs
1%).
- The most common serious adverse events
with CYRAMZA in Study 1 were anemia (3.8%) and intestinal
obstruction (2.1%). Red blood cell transfusions were given to 11%
of CYRAMZA-treated patients vs 8.7% of patients who received
placebo.
- Clinically relevant adverse reactions
reported in ≥1% and <5% of CYRAMZA-treated patients vs placebo
in Study 1 were: neutropenia (4.7% vs 0.9%), epistaxis (4.7% vs
0.9%), rash (4.2% vs 1.7%), intestinal obstruction (2.1% vs 0%),
and arterial thromboembolic events (1.7% vs 0%).
- Across clinical trials of CYRAMZA
administered as a single agent, clinically relevant adverse
reactions (including Grade ≥3) reported in CYRAMZA-treated patients
included proteinuria, gastrointestinal perforation, and
infusion-related reactions. In Study 1, according to laboratory
assessment, 8% of CYRAMZA-treated patients developed proteinuria vs
3% of placebo-treated patients. Two patients discontinued CYRAMZA
due to proteinuria. The rate of gastrointestinal perforation in
Study 1 was 0.8% and the rate of infusion-related reactions was
0.4%.
Most Common Adverse Reactions—Combination With
Paclitaxel
- The most commonly reported adverse
reactions (all grades; Grade 3/4) occurring in ≥5% of patients
receiving CYRAMZA plus paclitaxel and ≥2% higher than placebo plus
paclitaxel in Study 2 were fatigue/asthenia (57% vs 44%; 12% vs
6%), neutropenia (54% vs 31%; 41% vs 19%), diarrhea (32% vs 23%; 4%
vs 2%), epistaxis (31% vs 7%; 0% vs 0%), hypertension (25% vs 6%;
15% vs 3%), peripheral edema (25% vs 14%; 2% vs 1%), stomatitis
(20% vs 7%; 1% vs 1%), proteinuria (17% vs 6%; 1% vs 0%),
thrombocytopenia (13% vs 6%; 2% vs 2%), hypoalbuminemia (11% vs 5%;
1% vs 1%), and gastrointestinal hemorrhage events (10% vs 6%; 4% vs
2%).
- The most common serious adverse events
with CYRAMZA plus paclitaxel in Study 2 were neutropenia (3.7%) and
febrile neutropenia (2.4%); 19% of patients treated with CYRAMZA
plus paclitaxel received granulocyte colony-stimulating
factors.
- Adverse reactions resulting in
discontinuation of any component of the CYRAMZA plus paclitaxel
combination in 2% or more patients in Study 2 were neutropenia (4%)
and thrombocytopenia (3%).
- Clinically relevant adverse reactions
reported in ≥1% and <5% of the CYRAMZA plus paclitaxel-treated
patients in Study 2 were sepsis (3.1% for CYRAMZA plus paclitaxel
vs 1.8% for placebo plus paclitaxel) and gastrointestinal
perforations (1.2% for CYRAMZA plus paclitaxel vs 0.3% for placebo
plus paclitaxel).
Most Common Adverse Reactions—Combination With
Docetaxel
- The most commonly reported adverse
reactions (all grades; Grade 3/4) occurring in ≥5% of patients
receiving CYRAMZA plus docetaxel and ≥2% higher than placebo plus
docetaxel in Study 3 were neutropenia (55% vs 46%; 49% vs 40%),
fatigue/asthenia (55% vs 50%; 14% vs 11%), stomatitis/mucosal
inflammation (37% vs 19%; 7% vs 2%), epistaxis (19% vs 7%; <1%
vs <1%), febrile neutropenia (16% vs 10%; 16% vs 10%),
peripheral edema (16% vs 9%; 0% vs <1%), thrombocytopenia (13%
vs 5%; 3% vs <1%), lacrimation increased (13% vs 5%; <1% vs
0%), and hypertension (11% vs 5%; 6% vs 2%).
- The most common serious adverse events
with CYRAMZA plus docetaxel in Study 3 were febrile neutropenia
(14%), pneumonia (6%), and neutropenia (5%). The use of granulocyte
colony-stimulating factors was 42% in CYRAMZA plus
docetaxel-treated patients versus 37% in patients who received
placebo plus docetaxel.
- Treatment discontinuation due to
adverse reactions occurred more frequently in CYRAMZA plus
docetaxel-treated patients (9%) than in placebo plus
docetaxel-treated patients (5%). The most common adverse events
leading to treatment discontinuation of CYRAMZA in Study 3 were
infusion-related reaction (0.5%) and epistaxis (0.3%).
- Clinically relevant adverse reactions
reported in ≥1% and <5% of CYRAMZA plus docetaxel-treated
patients in Study 3 were hyponatremia (4.8% CYRAMZA plus docetaxel
versus 2.4% for placebo plus docetaxel) and proteinuria (3.3%
CYRAMZA plus docetaxel versus 0.8% placebo plus docetaxel).
Drug Interactions
- No pharmacokinetic (PK) interactions
were observed between ramucirumab (CYRAMZA) and paclitaxel or
between ramucirumab (CYRAMZA) and docetaxel.
Use in Specific Populations
- Pregnancy Category C: Based on its
mechanism of action, CYRAMZA may cause fetal harm. Advise females
of reproductive potential to avoid getting pregnant, including use
of adequate contraception, while receiving CYRAMZA and for at least
3 months after the last dose of CYRAMZA. Animal models link
angiogenesis, VEGF and VEGF Receptor 2 to critical aspects of
female reproduction, embryofetal development, and postnatal
development. There are no adequate or well-controlled studies of
ramucirumab in pregnant women. If this drug is used during
pregnancy, or if the patient becomes pregnant while taking this
drug, apprise the patient of the potential hazard to a fetus.
- Nursing Mothers: It is recommended to
discontinue nursing or discontinue CYRAMZA due to the potential
risks to the nursing infant.
- Females of Reproductive Potential:
Advise females of reproductive potential that CYRAMZA may impair
fertility.
Please see full Prescribing Information for
CYRAMZA, including Boxed Warning for hemorrhage.
RB-P HCP ISI 16DEC2014
Merck’s Focus on Cancer
Our goal is to translate breakthrough science into biomedical
innovations to help people with cancer worldwide. For Merck
Oncology, helping people fight cancer is our passion, supporting
accessibility to our cancer medicines is our commitment, and
pursuing research in immuno-oncology and other areas of
breakthrough science is our focus to potentially bring new hope to
people with cancer. For more information about our oncology
clinical trials, visit www.merck.com/clinicaltrials.
About Merck
Today’s Merck is a global healthcare leader working to help the
world be well. Merck is known as MSD outside the United States and
Canada. Through our prescription medicines, vaccines, biologic
therapies and animal health products, we work with customers and
operate in more than 140 countries to deliver innovative health
solutions. We also demonstrate our commitment to increasing access
to healthcare through far-reaching policies, programs and
partnerships. For more information, visit www.merck.com and connect
with us on Twitter, Facebook and YouTube.
About Lilly Oncology
For more than fifty years, Lilly has been dedicated to
delivering life-changing medicines and support to people living
with cancer and those who care for them. Lilly is determined to
build on this heritage and continue making life better for all
those affected by cancer around the world. To learn more about
Lilly's commitment to people with cancer, please visit
www.LillyOncology.com.
About Eli Lilly and Company
Lilly is a global healthcare leader that unites caring with
discovery to make life better for people around the world. We were
founded more than a century ago by a man committed to creating
high-quality medicines that meet real needs, and today we remain
true to that mission in all our work. Across the globe, Lilly
employees work to discover and bring life-changing medicines to
those who need them, improve the understanding and management of
disease, and give back to communities through philanthropy and
volunteerism. To learn more about Lilly, please visit us at
www.lilly.com and newsroom.lilly.com/social-channels.
C-LLY
RB93109 12/2014 © Lilly USA, LLC 2014. ALL RIGHTS
RESERVED.CYRAMZA® is a registered trademark of Eli Lilly and
Company.
Merck Forward-Looking Statement
This news release includes “forward-looking statements” within
the meaning of the safe harbor provisions of the United States
Private Securities Litigation Reform Act of 1995. These statements
are based upon the current beliefs and expectations of Merck’s
management and are subject to significant risks and uncertainties.
There can be no guarantees with respect to pipeline products that
the products will receive the necessary regulatory approvals or
that they will prove to be commercially successful. If underlying
assumptions prove inaccurate or risks or uncertainties materialize,
actual results may differ materially from those set forth in the
forward-looking statements.
Risks and uncertainties include, but are not limited to, general
industry conditions and competition; general economic factors,
including interest rate and currency exchange rate fluctuations;
the impact of pharmaceutical industry regulation and healthcare
legislation in the United States and internationally; global trends
toward healthcare cost containment; technological advances, new
products and patents attained by competitors; challenges inherent
in new product development, including obtaining regulatory
approval; Merck’s ability to accurately predict future market
conditions; manufacturing difficulties or delays; financial
instability of international economies and sovereign risk;
dependence on the effectiveness of Merck’s patents and other
protections for innovative products; and the exposure to
litigation, including patent litigation, and/or regulatory
actions.
Merck undertakes no obligation to publicly update any
forward-looking statement, whether as a result of new information,
future events or otherwise. Additional factors that could cause
results to differ materially from those described in the
forward-looking statements can be found in Merck’s 2013 Annual
Report on Form 10-K and the company’s other filings with the
Securities and Exchange Commission (SEC) available at the SEC’s
Internet site (www.sec.gov).
Lilly Forward-Looking Statement
This press release contains “forward-looking statements” (as
that term is defined in the United States Private Securities
Litigation Reform Act of 1995) regarding the research collaboration
between Merck and Lilly. This press release reflects Lilly's
current beliefs. However, there are substantial risks and
uncertainties in the process of drug research, development, and
commercialization. Among other risks, there can be no guarantee
that this investigational combination regimen will receive
regulatory approval, or, if approved, that it will achieve intended
benefits or become a commercially successful product. For further
discussion of these and other risks and uncertainties that could
cause actual results to differ materially from Lilly's
expectations, please see the company's latest Forms 10-K and 10-Q
filed with the U.S. Securities and Exchange Commission. Except as
required by law, Lilly undertakes no duty to update forward-looking
statements.
P-LLY
Photos/Multimedia Gallery Available:
http://www.businesswire.com/multimedia/home/20150113005234/en/
MerckMedia:Pamela Eisele, 267-305-3558Claire Mulhearn,
908-236-1118orInvestors:Justin Holko, 908-740-1879orLillyEli
Lilly and CompanyKeri McGrath, 317-277-3768Communications
Managermcgrath_happeks@lilly.com
Eli Lilly (NYSE:LLY)
Historical Stock Chart
From Apr 2024 to May 2024
Eli Lilly (NYSE:LLY)
Historical Stock Chart
From May 2023 to May 2024