On September 24, 2019 Eisai reported the presentation of new data and analyses via one oral proffered paper presentation, four poster discussions and seven poster presentations at the 2019 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Meeting from September 27 – October 1 in Barcelona, Spain (Press release, Eisai, SEP 24, 2019, View Source [SID1234539758]). Data to be presented include posters on the ongoing trials evaluating pembrolizumab plus lenvatinib in metastatic clear cell renal cell carcinoma (Poster #1187PD) and unresectable hepatocellular carcinoma (Poster #747P), as well as an oral presentation on the combination in advanced endometrial cancer (Poster #994O). Additionally, three Trials in Progress posters from the new LEAP (LEnvatinib And Pembrolizumab) clinical programs in three tumor types will also be presented: advanced urothelial carcinoma (Poster #990TiP), advanced or recurrent endometrial cancer (Poster #1063TiP) and advanced melanoma (Poster #1375TiP). Nine of the 11 planned potential pivotal trials under the LEAP program have been initiated to date; for more information, please visit clinicaltrials.gov.

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"We are pleased to share with our colleagues around the globe additional data on the pembrolizumab plus lenvatinib investigational combination across multiple cancer types," said Dr. Takashi Owa, Vice President, Chief Medicine Creation Officer and Chief Discovery Officer, Oncology Business Group. "As part of our human health care mission, we’re working to identify and develop solutions that help make a difference in the lives of people living with cancer. The data we will present – from increased response rates to real-world outcomes – demonstrate how we are working tirelessly to continually improve our understanding of our compounds and the patients we aim to serve."

Eisai will present an additional three posters on lenvatinib, including Phase 1/2 data on lenvatinib plus etoposide plus ifosfamide in patients with relapsed/refractory osteosarcoma (Poster #1676PD) and two studies in differentiated thyroid cancer, including a subgroup analysis of patients with lung metastasis in the SELECT pivotal trial (Poster #1862PD). Additionally, Eisai will present Phase 1 data on the liposomal formulation of eribulin (E7389-LF) in patients with advanced solid tumors (Poster #348P), as well as real world data on investigational uses for eribulin in patients with rare subtypes of soft-tissue sarcoma (Poster #1683P) and in patients with metastatic breast cancer with liver or lung metastasis (Poster #366P).

This release includes investigational compounds and uses for FDA-approved products. It is not intended to convey conclusions about efficacy and safety. There is no guarantee that any investigational compounds or uses of FDA-approved products will successfully complete clinical development or gain FDA approval.

The full list of Eisai presentations, along with the time and location of each session, is included below:

Abstract Title

Session (All times are Central European)

Lenvatinib

Phase 1 combination dose-finding/phase 2 expansion
cohorts of lenvatinib + etoposide + ifosfamide in patients
(pts) aged 2 to ≤25 years with relapsed/refractory (r/r)
osteosarcoma

Presentation #1676PD

Poster Discussion

Saturday, September 28

3:00-4:00 PM

Malaga Auditorium (Hall 5)

Nathalie Gaspar, MD

Lenvatinib and pembrolizumab in advanced endometrial
cancer

Presentation #994O

Proffered Paper

Sunday, September 29

9:30-9:45 AM

Madrid Auditorium (Hall 2)

Vicky Makker, MD

A phase 1b trial of lenvatinib (LEN) plus pembrolizumab
(PEMBRO) in unresectable hepatocellular carcinoma
(uHCC): Updated results

Presentation #747P

Poster Display

Sunday, September 29

12:00 – 1:00 PM

Poster Area (Hall 4)

Josep Lovett, MD

ENGOT-EN9/LEAP-001: a phase 3, randomized,
open-label study of pembrolizumab plus lenvatinib versus
chemotherapy for first-line treatment of advanced or
recurrent endometrial cancer

Presentation #1063TiP

Poster Display

Sunday, September 29

12:00 – 1:00 PM

Poster Area (Hall 4)

Christian Marth, PhD

Phase 2 study of lenvatinib plus pembrolizumab for
disease progression after PD-1/PD-L1 immune
checkpoint blockade in metastatic clear cell renal cell
carcinoma (mccRCC); Results of an interim analysis

Presentation #1187PD

Poster Discussion

Monday, September 30

8:45 – 9:45 AM

Malaga Auditorium (Hall 5)

Chung-Han Lee, MD, PhD

Impact of lung metastasis on overall survival in the phase
3 SELECT study with lenvatinib (LEN) in patients (pts)
with radioiodine refractory differentiated thyroid cancer
(RR-DTC)

Presentation #1862PD

Poster Discussion

Monday, September 30

10:30 – 11:30 AM

Cartagena Auditorium (Hall 3)

Makoto Tahara, MD, PhD

Prescription and Treatment Patterns of Lenvatinib (L) in
Patients with Radioactive Iodine-Refractory Differentiated
Thyroid Cancer (rDTC): A Retrospective Analysis of the
Canadian Patient Support Program (PSP)

Presentation #1863PD

Poster Discussion

Monday, September 30

10:30 – 11:30 AM

Cartagena Auditorium (Hall 3)

Sebastien J. Hotte, MD

Phase 3 LEAP-011: First-line Pembrolizumab (pembro)
with Lenvatinib (len) in patients (pts) with Advanced
Urothelial Carcinoma (UC) Ineligible to Receive
Platinum-Based chemotherapy (CT)

Presentation #990TiP

Poster Display

Monday, September 30

12:00 – 1:00 PM

Poster Area (Hall 4)

Yohann Loriot, MD, PhD

Pembrolizumab (pembro) Plus Lenvatinib (len) for
First‐Line Treatment of patients (pts) With Advanced
Melanoma: Phase 3 LEAP‐003 Study

Presentation #1375TiP

Poster Display

Monday, September 30

12:00 – 1:00 PM

Poster Area (Hall 4)

Alexander M. Eggermont, MD, PhD

Eribulin

One-year follow-up results of eribulin for soft-tissue
sarcoma including rare subtypes in a real-world
observational study in Japan

Presentation #1683P

Poster Display

Saturday, September 28

12:00 – 1:00 PM

Poster Area (Hall 4)

Shunji Takahashi, MD

Real-world 1-year survival analysis of patients
with metastatic breast cancer with liver or lung metastasis
treated with eribulin, gemcitabine or capecitabine

Presentation #366P

Poster Display

Sunday, September 29

12:00 – 1:00 PM

Poster Area (Hall 4)

Shayma M. Kazmi, MD

Phase 1 study of liposomal formulation of eribulin
(E7389-LF) in patients with advanced solid tumors:
primary results of dose escalation

Presentation #348P

Poster Display

Sunday, September 29

12:00 – 1:00 PM

Poster Area (Hall 4)

Noboru Yamamoto, MD, PhD

In March 2018, Eisai and Merck (known as MSD outside the United States and Canada), through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of lenvatinib, both as monotherapy and in combination with Merck’s anti-PD-1 therapy pembrolizumab.

About LENVIMA (lenvatinib) Capsules, 10 mg and 4 mg

LENVIMA is indicated:

For the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (RAI-refractory DTC)
In combination with everolimus for the treatment of patients with advanced renal cell carcinoma (RCC) following one prior anti-angiogenic therapy
For the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC)
In combination with pembrolizumab, for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior systemic therapy, and are not candidates for curative surgery or radiation. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial
Important Safety Information

Warnings and Precautions
Hypertension. In DTC, hypertension occurred in 73% of patients on LENVIMA (44% grade 3-4). In RCC, hypertension occurred in 42% of patients on LENVIMA + everolimus (13% grade 3). Systolic blood pressure ≥160 mmHg occurred in 29% of patients, and 21% had diastolic blood pressure ≥100 mmHg. In HCC, hypertension occurred in 45% of LENVIMA-treated patients (24% grade 3). Grade 4 hypertension was not reported in HCC.

Serious complications of poorly controlled hypertension have been reported. Control blood pressure prior to initiation. Monitor blood pressure after 1 week, then every 2 weeks for the first 2 months, and then at least monthly thereafter during treatment. Withhold and resume at reduced dose when hypertension is controlled or permanently discontinue based on severity.

Cardiac Dysfunction. Serious and fatal cardiac dysfunction can occur with LENVIMA. Across clinical trials in 799 patients with DTC, RCC, and HCC, grade 3 or higher cardiac dysfunction occurred in 3% of LENVIMA treated patients. Monitor for clinical symptoms or signs of cardiac dysfunction. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Arterial Thromboembolic Events. Among patients receiving LENVIMA or LENVIMA + everolimus, arterial thromboembolic events of any severity occurred in 2% of patients in RCC and HCC and 5% in DTC. Grade 3-5 arterial thromboembolic events ranged from 2% to 3% across all clinical trials. Permanently discontinue following an arterial thrombotic event. The safety of resuming after an arterial thromboembolic event has not been established and LENVIMA has not been studied in patients who have had an arterial thromboembolic event within the previous 6 months.

Hepatotoxicity. Across clinical studies enrolling 1,327 LENVIMA-treated patients with malignancies other than HCC, serious hepatic adverse reactions occurred in 1.4% of patients. Fatal events, including hepatic failure, acute hepatitis and hepatorenal syndrome, occurred in 0.5% of patients. In HCC, hepatic encephalopathy occurred in 8% of LENVIMA-treated patients (5% grade 3-5). Grade 3-5 hepatic failure occurred in 3% of LENVIMA-treated patients. 2% of patients discontinued LENVIMA due to hepatic encephalopathy and 1% discontinued due to hepatic failure.

Monitor liver function prior to initiation, then every 2 weeks for the first 2 months, and at least monthly thereafter during treatment. Monitor patients with HCC closely for signs of hepatic failure, including hepatic encephalopathy. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Renal Failure or Impairment. Serious including fatal renal failure or impairment can occur with LENVIMA. Renal impairment was reported in 14% and 7% of LENVIMA-treated patients in DTC and HCC, respectively. Grade 3-5 renal failure or impairment occurred in 3% of patients with DTC and 2% of patients with HCC, including 1 fatal event in each study. In RCC, renal impairment or renal failure was reported in 18% of LENVIMA + everolimus–treated patients (10% grade 3).

Initiate prompt management of diarrhea or dehydration/hypovolemia. Withhold and resume at reduced dose upon recovery or permanently discontinue for renal failure or impairment based on severity.

Proteinuria. In DTC and HCC, proteinuria was reported in 34% and 26% of LENVIMA-treated patients, respectively. Grade 3 proteinuria occurred in 11% and 6% in DTC and HCC, respectively. In RCC, proteinuria occurred in 31% of patients receiving LENVIMA + everolimus (8% grade 3). Monitor for proteinuria prior to initiation and periodically during treatment. If urine dipstick proteinuria ≥2+ is detected, obtain a 24-hour urine protein. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Diarrhea. Of the 737 LENVIMA-treated patients in DTC and HCC, diarrhea occurred in 49% (6% grade 3). In RCC, diarrhea occurred in 81% of LENVIMA + everolimus–treated patients (19% grade 3). Diarrhea was the most frequent cause of dose interruption/reduction, and diarrhea recurred despite dose reduction. Promptly initiate management of diarrhea. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Fistula Formation and Gastrointestinal Perforation. Of the 799 patients treated with LENVIMA or LENVIMA + everolimus in DTC, RCC, and HCC, fistula or gastrointestinal perforation occurred in 2%. Permanently discontinue in patients who develop gastrointestinal perforation of any severity or grade 3-4 fistula.

QT Interval Prolongation. In DTC, QT/QTc interval prolongation occurred in 9% of LENVIMA-treated patients and QT interval prolongation of >500 ms occurred in 2%. In RCC, QTc interval increases of >60 ms occurred in 11% of patients receiving LENVIMA + everolimus and QTc interval >500 ms occurred in 6%. In HCC, QTc interval increases of >60 ms occurred in 8% of LENVIMA-treated patients and QTc interval >500 ms occurred in 2%.

Monitor and correct electrolyte abnormalities at baseline and periodically during treatment. Monitor electrocardiograms in patients with congenital long QT syndrome, congestive heart failure, bradyarrhythmias, or those who are taking drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics. Withhold and resume at reduced dose upon recovery based on severity.

Hypocalcemia. In DTC, grade 3-4 hypocalcemia occurred in 9% of LENVIMA-treated patients. In 65% of cases, hypocalcemia improved or resolved following calcium supplementation with or without dose interruption or dose reduction. In RCC, grade 3-4 hypocalcemia occurred in 6% of LENVIMA + everolimus– treated patients. In HCC, grade 3 hypocalcemia occurred in 0.8% of LENVIMA-treated patients. Monitor blood calcium levels at least monthly and replace calcium as necessary during treatment. Withhold and resume at reduced dose upon recovery or permanently discontinue depending on severity.

Reversible Posterior Leukoencephalopathy Syndrome. Across clinical studies of 1,823 patients who received LENVIMA as a single agent, RPLS occurred in 0.3%. Confirm diagnosis of RPLS with MRI. Withhold and resume at reduced dose upon recovery or permanently discontinue depending on severity and persistence of neurologic symptoms.

Hemorrhagic Events. Serious including fatal hemorrhagic events can occur with LENVIMA. In DTC, RCC, and HCC clinical trials, hemorrhagic events, of any grade, occurred in 29% of the 799 patients treated with LENVIMA as a single agent or in combination with everolimus. The most frequently reported hemorrhagic events (all grades and occurring in at least 5% of patients) were epistaxis and hematuria. In DTC, grade 3-5 hemorrhage occurred in 2% of LENVIMA-treated patients, including 1 fatal intracranial hemorrhage among 16 patients who received LENVIMA and had CNS metastases at baseline. In RCC, grade 3-5 hemorrhage occurred in 8% of LENVIMA + everolimus–treated patients, including 1 fatal cerebral hemorrhage. In HCC, grade 3-5 hemorrhage occurred in 5% of LENVIMA-treated patients, including 7 fatal hemorrhagic events. Serious tumor-related bleeds, including fatal hemorrhagic events, occurred in LENVIMA-treated patients in clinical trials and in the postmarketing setting. In postmarketing surveillance, serious and fatal carotid artery hemorrhages were seen more frequently in patients with anaplastic thyroid carcinoma (ATC) than other tumors. Safety and effectiveness of LENVIMA in patients with ATC have not been demonstrated in clinical trials.

Consider the risk of severe or fatal hemorrhage associated with tumor invasion or infiltration of major blood vessels (eg, carotid artery). Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Impairment of Thyroid Stimulating Hormone Suppression/Thyroid Dysfunction. LENVIMA impairs exogenous thyroid suppression. In DTC, 88% of patients had baseline thyroid stimulating hormone (TSH) level ≤0.5 mU/L. In patients with normal TSH at baseline, elevation of TSH level >0.5 mU/L was observed post baseline in 57% of LENVIMA-treated patients. In RCC and HCC, grade 1 or 2 hypothyroidism occurred in 24% of LENVIMA + everolimus–treated patients and 21% of LENVIMA-treated patients, respectively. In patients with normal or low TSH at baseline, elevation of TSH was observed post baseline in 70% of LENVIMA-treated patients in HCC and 60% of LENVIMA + everolimus–treated patients in RCC.

Monitor thyroid function prior to initiation and at least monthly during treatment. Treat hypothyroidism according to standard medical practice.

Wound Healing Complications. Wound healing complications, including fistula formation and wound dehiscence, can occur with LENVIMA. Withhold for at least 6 days prior to scheduled surgery. Resume after surgery based on clinical judgment of adequate wound healing. Permanently discontinue in patients with wound healing complications.

Embryo-fetal Toxicity. Based on its mechanism of action and data from animal reproduction studies, LENVIMA can cause fetal harm when administered to pregnant women. In animal reproduction studies, oral administration of lenvatinib during organogenesis at doses below the recommended clinical doses resulted in embryotoxicity, fetotoxicity, and teratogenicity in rats and rabbits. Advise pregnant women of the potential risk to a fetus; and advise females of reproductive potential to use effective contraception during treatment with LENVIMA and for at least 30 days after the last dose.

Adverse Reactions
In DTC, the most common adverse reactions (≥30%) observed in LENVIMA-treated patients were hypertension (73%), fatigue (67%), diarrhea (67%), arthralgia/myalgia (62%), decreased appetite (54%), decreased weight (51%), nausea (47%), stomatitis (41%), headache (38%), vomiting (36%), proteinuria (34%), palmar-plantar erythrodysesthesia syndrome (32%), abdominal pain (31%), and dysphonia (31%). The most common serious adverse reactions (≥2%) were pneumonia (4%), hypertension (3%), and dehydration (3%). Adverse reactions led to dose reductions in 68% of LENVIMA-treated patients; 18% discontinued LENVIMA. The most common adverse reactions (≥10%) resulting in dose reductions were hypertension (13%), proteinuria (11%), decreased appetite (10%), and diarrhea (10%); the most common adverse reactions (≥1%) resulting in discontinuation of LENVIMA were hypertension (1%) and asthenia (1%).

In RCC, the most common adverse reactions (≥30%) observed in LENVIMA + everolimus–treated patients were diarrhea (81%), fatigue (73%), arthralgia/myalgia (55%), decreased appetite (53%), vomiting (48%), nausea (45%), stomatitis (44%), hypertension (42%), peripheral edema (42%), cough (37%), abdominal pain (37%), dyspnea (35%), rash (35%), decreased weight (34%), hemorrhagic events (32%), and proteinuria (31%). The most common serious adverse reactions (≥5%) were renal failure (11%), dehydration (10%), anemia (6%), thrombocytopenia (5%), diarrhea (5%), vomiting (5%), and dyspnea (5%). Adverse reactions led to dose reductions or interruption in 89% of patients. The most common adverse reactions (≥5%) resulting in dose reductions were diarrhea (21%), fatigue (8%), thrombocytopenia (6%), vomiting (6%), nausea (5%), and proteinuria (5%). Treatment discontinuation due to an adverse reaction occurred in 29% of patients.

In HCC, the most common adverse reactions (≥20%) observed in LENVIMA-treated patients were hypertension (45%), fatigue (44%), diarrhea (39%), decreased appetite (34%), arthralgia/myalgia (31%), decreased weight (31%), abdominal pain (30%), palmar-plantar erythrodysesthesia syndrome (27%), proteinuria (26%), dysphonia (24%), hemorrhagic events (23%), hypothyroidism (21%), and nausea (20%).

The most common serious adverse reactions (≥2%) were hepatic encephalopathy (5%), hepatic failure (3%), ascites (3%), and decreased appetite (2%). Adverse reactions led to dose reductions or interruption in 62% of patients. The most common adverse reactions (≥5%) resulting in dose reductions were fatigue (9%), decreased appetite (8%), diarrhea (8%), proteinuria (7%), hypertension (6%), and palmar-plantar erythrodysesthesia syndrome (5%). Treatment discontinuation due to an adverse reaction occurred in 20% of patients. The most common adverse reactions (≥1%) resulting in discontinuation of LENVIMA were fatigue (1%), hepatic encephalopathy (2%), hyperbilirubinemia (1%), and hepatic failure (1%).

In EC, the most common adverse reactions (≥20%) observed in LENVIMA + pembrolizumab – treated patients were fatigue (65%), hypertension (65%), musculoskeletal pain (65%), diarrhea (64%), decreased appetite (52%), hypothyroidism (51%), nausea (48%), stomatitis (43%), vomiting (39%), decreased weight (36%), abdominal pain (33%), headache (33%), constipation (32%), urinary tract infection (31%), dysphonia (29%), hemorrhagic events (28%), hypomagnesemia (27%), palmar-plantar erythrodysesthesia (26%), dyspnea (24%), cough (21%) and rash (21%).

Adverse reactions led to dose reduction or interruption in 88% of patients receiving LENVIMA. The most common adverse reactions (≥5%) resulting in dose reduction or interruption of LENVIMA were fatigue (32%), hypertension (26%), diarrhea (18%), nausea (13%), palmar-plantar erythrodysesthesia (13%), vomiting (13%), decreased appetite (12%), musculoskeletal pain (11%), stomatitis (9%), abdominal pain (7%), hemorrhages (7%), renal impairment (6%), decreased weight (6%), rash (5%), headache (5%), increased lipase (5%) and proteinuria (5%).

Fatal adverse reactions occurred in 3% of patients receiving LENVIMA + pembrolizumab, including gastrointestinal perforation, RPLS with intraventricular hemorrhage, and intracranial hemorrhage.

Serious adverse reactions occurred in 52% of patients receiving LENVIMA + pembrolizumab. Serious adverse reactions in ≥3% of patients were hypertension (9%), abdominal pain (6%), musculoskeletal pain (5%), hemorrhage (4%), fatigue (4%), nausea (4%), confusional state (4%), pleural effusion (4%), adrenal insufficiency (3%), colitis (3%), dyspnea (3%), and pyrexia (3%).

Permanent discontinuation due to adverse reaction (Grade 1-4) occurred in 21% of patients who received LENVIMA + pembrolizumab. The most common adverse reactions (>2%) resulting in discontinuation of LENVIMA were gastrointestinal perforation or fistula (2%), muscular weakness (2%), and pancreatitis (2%).

Use in Specific Populations
Because of the potential for serious adverse reactions in breastfed infants, advise women to discontinue breastfeeding during treatment and for at least 1 week after last dose. LENVIMA may impair fertility in males and females of reproductive potential.

No dose adjustment is recommended for patients with mild (CLcr 60-89 mL/min) or moderate (CLcr 30-59 mL/min) renal impairment. LENVIMA concentrations may increase in patients with DTC, RCC or EC and severe (CLcr 15-29 mL/min) renal impairment. Reduce the dose for patients with DTC, RCC, or EC and severe renal impairment. There is no recommended dose for patients with HCC and severe renal impairment. LENVIMA has not been studied in patients with end stage renal disease. No dose adjustment is recommended for patients with HCC and mild hepatic impairment (Child-Pugh A). There is no recommended dose for patients with HCC with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment.

No dose adjustment is recommended for patients with DTC, RCC, or EC and mild or moderate hepatic impairment. LENVIMA concentrations may increase in patients with DTC, RCC, or EC and severe hepatic impairment. Reduce the dose for patients with DTC, RCC, or EC and severe hepatic impairment.

Please see Prescribing Information for LENVIMA (lenvatinib) at View Source

About HALAVEN (eribulin mesylate) Injection
HALAVEN (eribulin mesylate) Injection is a microtubule dynamics inhibitor indicated for the treatment of patients with:

Metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting.
Unresectable or metastatic liposarcoma who have received a prior anthracycline-containing regimen.
Discovered and developed by Eisai, eribulin is a synthetic analog of halichondrin B, a natural product that was isolated from the marine sponge Halichondria okadai. First in the halichondrin class, HALAVEN is a microtubule dynamics inhibitor. Eribulin is believed to work primarily via a tubulin-based mechanism that causes prolonged and irreversible mitotic blockage, ultimately leading to apoptotic cell death. Additionally, in preclinical studies of human breast cancer, eribulin demonstrated complex effects on the tumor biology of surviving cancer cells, including increases in vascular perfusion resulting in reduced tumor hypoxia, and changes in the expression of genes in tumor specimens associated with a change in phenotype, promoting the epithelial phenotype, opposing the mesenchymal phenotype. Eribulin has also been shown to decrease the migration and invasiveness of human breast cancer cells.

Important Safety Information

Warnings and Precautions
Neutropenia: Severe neutropenia (ANC <500/mm3) lasting >1 week occurred in 12% of patients with mBC and liposarcoma or leiomyosarcoma. Febrile neutropenia occurred in 5% of patients with mBC and 2 patients (0.4%) died from complications. Febrile neutropenia occurred in 0.9% of patients with liposarcoma or leiomyosarcoma, and fatal neutropenic sepsis occurred in 0.9% of patients. Patients with mBC with elevated liver enzymes >3 × ULN and bilirubin >1.5 × ULN experienced a higher incidence of Grade 4 neutropenia and febrile neutropenia than patients with normal levels. Monitor complete blood cell counts prior to each dose, and increase the frequency of monitoring in patients who develop Grade 3 or 4 cytopenias. Delay administration and reduce subsequent doses in patients who experience febrile neutropenia or Grade 4 neutropenia lasting >7 days.

Peripheral Neuropathy: Grade 3 peripheral neuropathy occurred in 8% of patients with mBC (Grade 4=0.4%) and 22% developed a new or worsening neuropathy that had not recovered within a median follow-up duration of 269 days (range 25-662 days). Neuropathy lasting >1 year occurred in 5% of patients with mBC. Grade 3 peripheral neuropathy occurred in 3.1% of patients with liposarcoma and leiomyosarcoma receiving HALAVEN and neuropathy lasting more than 60 days occurred in 58% (38/65) of patients who had neuropathy at the last treatment visit. Patients should be monitored for signs of peripheral motor and sensory neuropathy. Withhold HALAVEN in patients who experience Grade 3 or 4 peripheral neuropathy until resolution to Grade 2 or less.

Embryo-Fetal Toxicity: HALAVEN can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with HALAVEN and for at least 2 weeks following the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with HALAVEN and for 3.5 months following the final dose.

QT Prolongation: Monitor for prolonged QT intervals in patients with congestive heart failure, bradyarrhythmias, drugs known to prolong the QT interval, and electrolyte abnormalities. Correct hypokalemia or hypomagnesemia prior to initiating HALAVEN and monitor these electrolytes periodically during therapy. Avoid in patients with congenital long QT syndrome.

Adverse Reactions
In patients with mBC receiving HALAVEN, the most common adverse reactions (≥25%) were neutropenia (82%), anemia (58%), asthenia/fatigue (54%), alopecia (45%), peripheral neuropathy (35%), nausea (35%), and constipation (25%). Febrile neutropenia (4%) and neutropenia (2%) were the most common serious adverse reactions. The most common adverse reaction resulting in discontinuation was peripheral neuropathy (5%).

In patients with liposarcoma and leiomyosarcoma receiving HALAVEN, the most common adverse reactions (≥25%) reported in patients receiving HALAVEN were fatigue (62%), nausea (41%), alopecia (35%), constipation (32%), peripheral neuropathy (29%), abdominal pain (29%), and pyrexia (28%). The most common (≥5%) Grade 3-4 laboratory abnormalities reported in patients receiving HALAVEN were neutropenia (32%), hypokalemia (5.4%), and hypocalcemia (5%). Neutropenia (4.9%) and pyrexia (4.5%) were the most common serious adverse reactions. The most common adverse reactions resulting in discontinuation were fatigue and thrombocytopenia (0.9% each).

Use in Specific Populations
Lactation: Because of the potential for serious adverse reactions in breastfed infants from eribulin mesylate, advise women not to breastfeed during treatment with HALAVEN and for 2 weeks after the final dose.

Hepatic and Renal Impairment: A reduction in starting dose is recommended for patients with mild or moderate hepatic impairment and/or moderate or severe renal impairment.

For more information about HALAVEN, click here for the full Prescribing Information.

About the Eisai and Merck Strategic Collaboration
In March 2018, Eisai and Merck, known as MSD outside the United States and Canada, through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of LENVIMA (lenvatinib). Under the agreement, the companies will jointly develop, manufacture and commercialize LENVIMA, both as monotherapy and in combination with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab).

In addition to ongoing clinical studies evaluating the KEYTRUDA plus LENVIMA combination across several different tumor types, including renal cell carcinoma, the companies will jointly initiate new clinical studies through the LEAP (LEnvatinib And Pembrolizumab) clinical program, which will evaluate the combination to support 11 potential indications in six types of cancer (endometrial cancer, hepatocellular carcinoma, melanoma, non-small cell lung cancer, squamous cell carcinoma of the head and neck, and urothelial cancer). The LEAP clinical program also includes a new basket trial targeting six additional cancer types (biliary tract cancer, breast cancer, colorectal cancer, gastric cancer, glioblastoma and ovarian cancer).

On September 24, 2019 Neogen Corporation (Nasdaq: NEOG) reported that revenues for the first quarter of its 2020 fiscal year, which ended Aug. 31, were $101,424,000, compared to the previous year’s first quarter revenues of $99,626,000 (Press release, Neogen, SEP 24, 2019, View Source [SID1234539757]).

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The first quarter was the 110th of the past 115 quarters that Neogen reported revenue increases compared with the previous year — including all consecutive quarters in the last 14 years.

Net income for the first quarter of Neogen’s 2020 fiscal year was $14,652,000, or $0.28 per share, compared to $15,237,000, or $0.29 per share, in the previous year’s first quarter. In the prior year’s first quarter, Neogen benefitted from higher tax deductions relating to employee stock option exercises, which contributed to an effective tax rate of 11% for the quarter. In the first quarter of the current year, Neogen’s effective tax rate was 17%.

"Our first quarter did not meet the overall performance expectations that we have for ourselves. Even considering the difficult international business climate created by the continuing strong U.S. dollar and the U.S. trade issues with China and elsewhere, we must work to produce better results," said John Adent, Neogen’s president and chief executive officer. "We were, however, pleased with the continued strength of our genomics business, and we are continuing to build upon our core strengths to return to our historic growth rates, while also expanding our capabilities.

"In August, we announced a licensing agreement with Corvium, a leading producer of risk management software for the food safety industry, that will complement our diagnostics business by efficiently providing our customers with the information they need to make rapid data-driven decisions to protect their consumers and businesses," Adent continued. "We have also continued our genomics laboratory expansions in China, Brazil Canada and the United Kingdom, and are in the beginning stages of an expansion at our flagship operation in Lincoln, Neb., as we work to satisfy the accelerating demand for our genomics services."

Neogen’s gross margin was 47.5% of sales in the first quarter of the current fiscal year, compared to 46.9% recorded in the same period a year ago, driven by improved gross margins in the domestic genomics business, and a favorable mix shift in Food Safety towards higher margin products. Operating income for the quarter was $16,264,000, or 16.0% of sales, compared to $16,479,000, or 16.5%, a year ago, with the decline largely the result of increased spending in new product development.

"The first quarter saw a continuation of the adverse currency environment that we experienced in each of the four quarters of our previous fiscal year. In the current quarter, we would have recorded approximately $1.2 million more in revenues in a neutral currency environment," said Steve Quinlan, Neogen’s chief financial officer. "At the bottom line, we knew we faced a difficult comparison with the prior year quarter’s exceptionally low effective tax rate, which was impacted by the exercise of stock options by company employees. The timing and amount of these exercises will continue to impact the company’s effective rate going forward. But, as shown on our balance sheet, our strong cash position provides great flexibility to continue to invest in our businesses going forward."

Revenues for the company’s Food Safety segment were $51,021,000 in the current quarter, compared to $52,183,000 in the prior year’s first three months. The decrease was due primarily to lower sales internationally, caused in part by the continued strong U.S. dollar. As the majority of Neogen’s international locations report through the company’s Food Safety segment, adverse currency translations are primarily reflected in this segment’s revenue results.

Revenues at the company’s Brazilian operations decreased 16% in the current quarter compared to the prior year in U.S. dollars, as losses in sales of biosecurity products and forensic test kits were offset only partially by increases in sales of mycotoxin test kits, dairy residue test kits and culture media. The decrease in biosecurity sales was the result of a non-recurring government tender in Brazil in the prior year first quarter, while the decline in forensic test kits revenues was due to the loss of a large commercial lab customer that performs drug testing of truck and bus drivers in that country.

Mexico-based Neogen Latinoamerica’s sales increased 5% in U.S. dollars, due to strong increases in sales of mycotoxin and pathogen test kits, and dehydrated culture media; these increases were somewhat offset by lower sales of rodenticides and disinfectants. Revenues at our European operations rose 1% in local currency, as increases in cleaners and disinfectants were partially offset by lower sales in the culture media, spoilage organism and foodborne pathogen product lines, but decreased 4% when converted to U.S. dollars. In China, the African swine fever outbreak in that country resulted in lower genomic testing to the pork markets, and contributed to an 18% decline in revenues.

Global sales of Neogen’s natural toxin test kits increased 9% in the current quarter, led by a 23% increase in sales to detect aflatoxin. The quarterly increase in aflatoxin test kit sales was largely driven by increased market share gains in Brazil and Mexico during the corn harvest. Because of a relatively wet spring in the U.S., testing of domestic grain crops has largely been delayed.

Sales of Neogen’s rapid tests to detect the foodborne pathogen Listeria, including the innovative Listeria Right Now test system, increased 20% in the quarter compared to the prior year. Listeria Right Now detects the pathogen in less than an hour — without the otherwise necessary incubation time of 24 to 48 hours. Sales of Neogen’s sanitation test systems, which includes its AccuPoint Advanced ATP Sanitation Monitoring System, increased 12% in the current quarter when compared to the prior year, and the company’s test kits to detect foodborne allergens increased 8% compared to the previous year’s first quarter.

Neogen’s Animal Safety segment reported revenues of $50,403,000 for the first quarter of the 2020 fiscal year, compared to $47,443,000 in the prior year first quarter, an increase of 6%. The segment’s highlights in the quarter included strong growth in the domestic genomics testing business, a 10% increase in sales of the company’s animal care products, and a 9% increase in veterinary instruments. These increases were partially offset by lower sales of certain rodenticides.

Revenues from Neogen’s worldwide animal genomics business increased 17% in the first quarter of fiscal 2020 compared to the prior year. This growth was primarily the result of continued strength in the company’s bovine business, which includes commercial beef and dairy product lines. The increase was also the result of Neogen’s accelerating growth in companion animal genetic testing, including tests for dog and cat parentage, breed verification, and genetic health.

Neogen Corporation develops and markets products dedicated to food and animal safety. The company’s Food Safety Division markets dehydrated culture media and diagnostic test kits to detect foodborne bacteria, natural toxins, food allergens, drug residues, plant diseases and sanitation concerns. Neogen’s Animal Safety Division is a leader in worldwide biosecurity products, animal genomics testing and the manufacturing and distribution of a variety of animal healthcare products, including diagnostics, pharmaceuticals and veterinary instruments.

Certain portions of this news release that do not relate to historical financial information constitute forward-looking statements. These forward-looking statements are subject to certain risks and uncertainties. Actual future results and trends may differ materially from historical results or those expected depending on a variety of factors listed in Management’s Discussion and Analysis of Financial Condition and Results of Operations in the Company’s most recently filed Form 10-K.

On September 24, 2019 SkylineDx reported at the 32nd Biennial Dermatology Symposium: The O’Leary Meeting 2019 in Rochester (MN, US) the launch of a pilot study it will conduct with the Mayo Clinic to evaluate and optimize its diagnostic services focused on primary cutaneous melanoma (skin cancer) (Press release, SkylineDx, SEP 24, 2019, View Source [SID1234539756]). SkylineDx’ proprietary diagnostic test combines genetic information from a patient’s tumor cells (taken during a diagnostic biopsy) with tumor – and patient specific characteristics. Put together, the test can accurately predict the risk of regional metastasis at the time of melanoma diagnosis. Currently, based on tumor characteristics alone, too many patients are predicted to have metastasis at diagnosis which results in many unneeded surgical interventions, so-called sentinel lymph node biopsies. The SkylineDx diagnostic test identifies patients who can safely forgo this surgical intervention. This pilot study with Mayo Clinic is an usability evaluation and the final step before starting a national trial in the United States in 2020.

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This announcement follows the joint development agreement that SkylineDx and Mayo Clinic signed in 2018. "In the last 18 months we have been working with the research group of Alexander Meves M.D., a dermatologist of Mayo Clinic, to fully optimize and develop the test", says Dharminder Chahal, CEO SkylineDx. This extensive collaboration has been part of the Falcon Research & Development Program. As the falcon is known as an intelligent creature with unprecedented senses and skills, this R&D program is uniquely equipped to unveil new, detailed insights in the genomic, pathologic and clinical nature of melanoma. "With melanoma being the deadliest form of skin cancer, the launch of this Falcon Research & Development Program will make an important and much needed contribution to improving patient outcomes in this field," continues Dharminder Chahal.

Under the wings of the Falcon R&D Program, a series of specific studies and projects are initiated to demonstrate clinical utility, aimed at developing and introducing an array of diagnostic utilities, ready for the patient. The first focus area is called the Merlin Study Initiative, which covers clinical research and validation studies for the test that predicts if a patient can safely avoid sentinel lymph node surgery. Furthermore, under the Peregrine Study Initiative, SkylineDx is in advanced stages of research to develop a test that predicts a patient’s prognosis and identifies patients that are likely to progress faster and might benefit from early adjuvant therapy.

Dr. Meves and Mayo Clinic have financial interest in the test referenced in this release. Mayo Clinic will use any revenue it receives to support its not-for-profit mission in patient care, education and research.

On September 24, 2019 Linnaeus Therapeutics, Inc. (Linnaeus), a privately held, clinical-stage biopharmaceutical company focused on the development and commercialization of novel, small molecule oncology therapeutics, reported that the U.S. Food and Drug Administration (FDA) has cleared the company’s investigational new drug application (IND) for LNS8801, a small molecule agonist of the G protein-coupled estrogen receptor (GPER) (Press release, Linnaeus Therapeutics, SEP 24, 2019, View Source [SID1234539755]). Linnaeus is developing LNS8801 for the treatment of solid and hematologic cancers.

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"The FDA clearance of the IND allows Linnaeus to begin human testing of LNS8801 and represents the culmination of a tremendous effort by our research and development team," commented Patrick Mooney, MD, chief executive officer of Linnaeus. "LNS8801 is a potent and highly selective small molecule agonist of GPER. Based on the epidemiological evidence and the strong preclinical data, we believe that LNS8801 has very real potential to provide meaningful and lasting clinical benefit for patients with cancer. We are excited to enroll our first patient in the coming weeks."

FDA allowance of the IND enables Linnaeus to initiate its planned phase 1/2 clinical trial in patients with advanced cancers. The phase 1 dose-escalation portion of the trial will assess the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of LNS8801. After a recommended phase 2 dose is established, dose expansion cohorts are anticipated. Linnaeus expects the first patient to be enrolled in the trial in October 2019.

About LNS8801
LNS8801 is an orally bioavailable, highly specific, agonist of GPER whose activity is dependent on the expression of GPER. GPER activation suppresses well-known tumor associated genes, such as c-Myc and PD-L1. In preclinical cancer models, LNS8801 displays potent antitumor activities across a wide range of tumor types, rapidly shrinking tumors and inducing immune memory. LNS8801 monotherapy has significant antitumor activity, including complete responses that are immune to rechallenge. LNS8801 also has combinatorial effects with targeted therapies and immunotherapies. Preclinical toxicology studies have established a wide safety margin.

On September 24, 2019 Amgen (NASDAQ:AMGN) reported that the results of a prespecified interim analysis of an open-label, randomized, controlled global multicenter Phase 3 trial (20120215) showed that the primary endpoint of event-free survival was met (Press release, Amgen, SEP 24, 2019, View Source [SID1234539754]). The study evaluated the efficacy, safety and tolerability of BLINCYTO (blinatumomab) compared to conventional consolidation chemotherapy in pediatric patients with high-risk, B-cell acute lymphoblastic leukemia (ALL) at first relapse. Enrollment was terminated early due to encouraging efficacy in the BLINCYTO arm and was based on a recommendation from the Independent Data Monitoring Committee (DMC). Follow up will continue as prescribed per protocol.

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In addition, a randomized, Phase 3 trial (AALL1331) conducted by the Children’s Oncology Group (COG) using BLINCYTO in pediatric B-cell ALL patients at first relapse has closed to accrual for the high-risk and intermediate risk-arm based on the recommendation of the COG DMC. The DMC closure decision was based on a strong trend towards improved disease-free survival and improved overall survival, markedly lower toxicity, and better minimal residual disease (MRD) clearance for BLINCYTO compared to chemotherapy. The COG DMC recommended that the AALL1331 low-risk group continue to enroll and randomize patients until enrollment goals are reached. AALL1331 is sponsored by the Cancer Therapy Evaulation Program of the National Cancer Institute (NCI), part of the National Institutes of Health, and is conducted by the NCI-funded COG. Amgen provided BLINCYTO for AALL1331 under a Collaborative Research and Development Agreement between the NCI and Amgen.

"Considered together, the results of these studies are remarkable. Children and adolescents who relapse with acute lymphoblastic leukemia face a poor prognosis and there remains a need for additional treatment options, particularly for those that are identified as high-risk. These data have the potential to be practice-changing and may provide a treatment approach to prevent further relapse that is superior to chemotherapy," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "We look forward to discussing these data with regulatory authorities."

The BLINCYTO adverse events observed in the Phase 3 20120215 and the COG AALL1331 studies were consistent with the known safety profile of BLINCYTO. These interim data will be submitted to a future medical conference and for publication.

About the 20120215 Study

Study 20120215 is a Phase 3 open-label, multicenter, randomized, controlled trial to evaluate event-free survival after treatment with BLINCYTO compared with standard of care consolidation chemotherapy in pediatric patients with high-risk first relapsed B-cell ALL. Key secondary endpoints included incidence of overall survival and MRD response, AEs, 100-day mortality after alloHSCT, incidence of anti-blinatumomab antibody formation, cumulative incidence of relapse. This is a global study that is being conducted as part of the PIP (Pediatric Investigation Plan) agreed to between Amgen and the EMA. The study is being conducted in Australia and various countries in EU and Latin America. Click here to read about the trial on ClinicalTrials.gov.

About the COG AALL1331 Study

The COG AALL1331 study is a risk-stratified, randomized, Phase 3 trial of blinatumomab in first relapse of pediatric B-ALL to evaluate disease-free survival (DFS) of high-risk (HR) and intermediate-risk (IR) relapsed B-ALL patients who are randomized following induction block 1 chemotherapy to receive either two intensive chemotherapy blocks or two 5-week blocks of blinatumomab. It also compares the DFS of low risk (LR) relapse B-ALL patients who are randomized following block 1 chemotherapy to receive either chemotherapy alone or chemotherapy plus blinatumomab. Key secondary endpoints include overall survival of HR, IR, and LR relapsed B-ALL patients. This is a global study that is being conducted in Australia, Canada, New Zealand and United States. Click here to read about the trial on ClinicalTrials.gov.

About BLINCYTO (blinatumomab)

BLINCYTO is a bispecific CD19-directed CD3 T cell engager (BiTE) antibody construct that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.

BiTE antibody constructs are a type of immunotherapy being investigated for fighting cancer by helping the body’s immune system to detect and target malignant cells. The modified antibodies are designed to engage two different targets simultaneously, thereby juxtaposing T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. BiTE antibody constructs help place the T cells within reach of the targeted cell, with the intent of allowing T cells to inject toxins and trigger the cancer cell to die (apoptosis). BiTE antibody constructs are currently being investigated for their potential to treat a wide variety of cancers.

BLINCYTO was granted breakthrough therapy and priority review designations by the U.S. Food and Drug Administration and is approved in the U.S. for the treatment of:

relapsed or refractory B-cell precursor ALL in adults and children.
B-cell precursor ALL in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1% in adults and children.
This indication is approved under accelerated approval based on MRD response rate and hematological relapse-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
In the EU, BLINCYTO is indicated as monotherapy for the treatment of:

adults with Philadelphia chromosome negative CD19 positive relapsed or refractory B-precursor acute lymphoblastic leukaemia (ALL).
adults with Philadelphia chromosome negative CD19 positive B-precursor ALL in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1%.
paediatric patients aged 1 year or older with Philadelphia chromosome negative CD19 positive B-precursor ALL which is refractory or in relapse after receiving at least two prior therapies or in relapse after receiving prior allogeneic hematopoietic stem cell transplantation
About BiTE Technology

Bispecific T cell engager (BiTE) technology is a targeted immuno-oncology platform designed to engage patients’ own T cells to any tumor-specific antigen, activating the cytotoxic potential of T cells to eliminate detectable cancer. BiTE antibody constructs are currently being investigated for their potential to treat a wide variety of cancers. For more information, visit www.biteantibodies.com.

IMPORTANT SAFETY INFORMATION

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES

Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO and treat with corticosteroids as recommended.
Neurological toxicities, which may be severe, life-threatening or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO as recommended.
Contraindications

BLINCYTO is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.

Warnings and Precautions

Cytokine Release Syndrome (CRS): CRS, which may be life-threatening or fatal, occurred in 15% of patients with R/R ALL and in 7% of patients with MRD-positive ALL. The median time to onset of CRS is 2 days after the start of infusion and the median time to resolution of CRS was 5 days among cases that resolved. Closely monitor and advise patients to contact their healthcare professional for signs and symptoms of serious adverse events such as fever, headache, nausea, asthenia, hypotension, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased total bilirubin (TBILI), and disseminated intravascular coagulation (DIC). The manifestations of CRS after treatment with BLINCYTO overlap with those of infusion reactions, capillary leak syndrome, and hemophagocytic histiocytosis/macrophage activation syndrome. If severe CRS occurs, interrupt BLINCYTO until CRS resolves. Discontinue BLINCYTO permanently if life-threatening CRS occurs. Administer corticosteroids for severe or life-threatening CRS.
Neurological Toxicities: Approximately 65% of patients receiving BLINCYTO in clinical trials experienced neurological toxicities. The median time to the first event was within the first 2 weeks of BLINCYTO treatment and the majority of events resolved. The most common (≥ 10%) manifestations of neurological toxicity were headache and tremor. Severe, life‐threatening, or fatal neurological toxicities occurred in approximately 13% of patients, including encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders. Manifestations of neurological toxicity included cranial nerve disorders. Monitor patients for signs or symptoms and interrupt or discontinue BLINCYTO as outlined in the PI.
Infections: Approximately 25% of patients receiving BLINCYTO in clinical trials experienced serious infections such as sepsis, pneumonia, bacteremia, opportunistic infections, and catheter-site infections, some of which were life-threatening or fatal. Administer prophylactic antibiotics and employ surveillance testing as appropriate during treatment. Monitor patients for signs or symptoms of infection and treat appropriately, including interruption or discontinuation of BLINCYTO as needed.
Tumor Lysis Syndrome (TLS), which may be life-threatening or fatal, has been observed. Preventive measures, including pretreatment nontoxic cytoreduction and on-treatment hydration, should be used during BLINCYTO treatment. Monitor patients for signs and symptoms of TLS and interrupt or discontinue BLINCYTO as needed to manage these events.
Neutropenia and Febrile Neutropenia, including life-threatening cases, have been observed. Monitor appropriate laboratory parameters (including, but not limited to, white blood cell count and absolute neutrophil count) during BLINCYTO infusion and interrupt BLINCYTO if prolonged neutropenia occurs.
Effects on Ability to Drive and Use Machines: Due to the possibility of neurological events, including seizures, patients receiving BLINCYTO are at risk for loss of consciousness, and should be advised against driving and engaging in hazardous occupations or activities such as operating heavy or potentially dangerous machinery while BLINCYTO is being administered.
Elevated Liver Enzymes: Transient elevations in liver enzymes have been associated with BLINCYTO treatment with a median time to onset of 3 days. In patients receiving BLINCYTO, although the majority of these events were observed in the setting of CRS, some cases of elevated liver enzymes were observed outside the setting of CRS, with a median time to onset of 19 days. Grade 3 or greater elevations in liver enzymes occurred in approximately 7% of patients outside the setting of CRS and resulted in treatment discontinuation in less than 1% of patients. Monitor ALT, AST, gamma-glutamyl transferase, and TBILI prior to the start of and during BLINCYTO treatment. BLINCYTO treatment should be interrupted if transaminases rise to > 5 times the upper limit of normal (ULN) or if TBILI rises to > 3 times ULN.
Pancreatitis: Fatal pancreatitis has been reported in patients receiving BLINCYTO in combination with dexamethasone in clinical trials and the post-marketing setting. Evaluate patients who develop signs and symptoms of pancreatitis and interrupt or discontinue BLINCYTO and dexamethasone as needed.
Leukoencephalopathy: Although the clinical significance is unknown, cranial magnetic resonance imaging (MRI) changes showing leukoencephalopathy have been observed in patients receiving BLINCYTO, especially in patients previously treated with cranial irradiation and antileukemic chemotherapy.
Preparation and administration errors have occurred with BLINCYTO treatment. Follow instructions for preparation (including admixing) and administration in the PI strictly to minimize medication errors (including underdose and overdose).
Immunization: Vaccination with live virus vaccines is not recommended for at least 2 weeks prior to the start of BLINCYTO treatment, during treatment, and until immune recovery following last cycle of BLINCYTO.
Risk of Serious Adverse Reactions in Pediatric Patients due to Benzyl Alcohol Preservative: Serious and fatal adverse reactions including "gasping syndrome," which is characterized by central nervous system depression, metabolic acidosis, and gasping respirations, can occur in neonates and infants treated with benzyl alcohol-preserved drugs including BLINCYTO (with preservative). When prescribing BLINCYTO (with preservative) for pediatric patients, consider the combined daily metabolic load of benzyl alcohol from all sources including BLINCYTO (with preservative) and other drugs containing benzyl alcohol. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known. Due to the addition of bacteriostatic saline, 7-day bags of BLINCYTO solution for infusion with preservative contain benzyl alcohol and are not recommended for use in any patients weighing < 22 kg.
Adverse Reactions

The most common adverse reactions (≥ 20%) in clinical trial experience of patients with MRD-positive B-cell precursor ALL (BLAST Study) treated with BLINCYTO were pyrexia (91%), infusion-related reactions (77%), headache (39%), infections (pathogen unspecified [39%]), tremor (31%), and chills (28%). Serious adverse reactions were reported in 61% of patients. The most common serious adverse reactions (≥ 2%) included pyrexia, tremor, encephalopathy, aphasia, lymphopenia, neutropenia, overdose, device related infection, seizure, and staphylococcal infection.
The most common adverse reactions (≥ 20%) in clinical trial experience of patients with Philadelphia chromosome-negative relapsed or refractory B-cell precursor ALL (TOWER Study) treated with BLINCYTO were infections (bacterial and pathogen unspecified), pyrexia, headache, infusion-related reactions, anemia, febrile neutropenia, thrombocytopenia, and neutropenia. Serious adverse reactions were reported in 62% of patients. The most common serious adverse reactions (≥ 2%) included febrile neutropenia, pyrexia, sepsis, pneumonia, overdose, septic shock, CRS, bacterial sepsis, device related infection, and bacteremia.
Adverse reactions that were observed more frequently (≥ 10%) in the pediatric population compared to the adults with relapsed or refractory B-cell precursor ALL were pyrexia (80% vs. 61%), hypertension (26% vs. 8%), anemia (41% vs. 24%), infusion-related reaction (49% vs. 34%), thrombocytopenia (34% vs. 21%), leukopenia (24% vs. 11%), and weight increased (17% vs. 6%).
In pediatric patients less than 2 years old (infants), the incidence of neurologic toxicities was not significantly different than for the other age groups, but its manifestations were different; the only event terms reported were agitation, headache, insomnia, somnolence, and irritability. Infants also had an increased incidence of hypokalemia (50%) compared to other pediatric age cohorts (15-20%) or adults (17%).
Dosage and Administration Guidelines

BLINCYTO is administered as a continuous intravenous infusion at a constant flow rate using an infusion pump which should be programmable, lockable, non-elastomeric, and have an alarm.
It is very important that the instructions for preparation (including admixing) and administration provided in the full Prescribing Information are strictly followed to minimize medication errors (including underdose and overdose).
Please see full Prescribing Information and medication guide for BLINCYTO at www.BLINCYTO.com.

About Amgen Oncology

Amgen Oncology is searching for and finding answers to incredibly complex questions that will advance care and improve lives for cancer patients and their families. Our research drives us to understand the disease in the context of the patient’s life – not just their cancer journey – so they can take control of their lives.

For the last four decades, we have been dedicated to discovering the firsts that matter in oncology and to finding ways to reduce the burden of cancer. Building on our heritage, Amgen continues to advance the largest pipeline in the Company’s history, moving with great speed to advance those innovations for the patients who need them.

At Amgen, we are driven by our commitment to transform the lives of cancer patients and keep them at the center of everything we do.

For more information, follow us on www.twitter.com/amgenoncology.