On January 19, 2018 Celgene Corporation (NASDAQ: CELG) reported primary endpoint findings and updated results of secondary endpoints from the phase II international LAPACT trial of ABRAXANE (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) plus gemcitabine in patients with locally advanced pancreatic cancer (Press release, Celgene, JAN 19, 2018, View Source [SID1234523366]). The results were presented today at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO GI) in San Francisco, California.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

An analysis of patients with newly diagnosed, locally advanced pancreatic cancer treated with up to 6 cycles of ABRAXANE + gemcitabine as an investigational induction therapy (n=106) found that patients had a median time to treatment failure (TTF) of 8.8 months (90% CI: 6.67-9.82), which exceeded the protocol-specified target of 6.6 months (primary endpoint). Secondary endpoints included evaluation of the disease control rate (DCR), overall response rate (ORR), progression free survival (PFS) and overall survival (OS) in patients treated with an ABRAXANE + gemcitabine induction therapy. The updated analysis found a 77.6% DCR ≥ 16 wks (DCR ≥ 16 wks: stable disease (SD) ≥ 16 wks = 44.9%, CR = 0%, PR = 32%) and 65.4% DCR ≥ 24 wks (DCR ≥ 24 wks: SD ≥ 24 wks = 32.7%, CR = 0%, PR = 32%). The ORR was 32% (CR=0%, PR=32%), the median PFS was 10.8 months (9,26-11.63; 90% CI) and 12-month estimated OS was 72% (64.5% – 78.9%; 90% CI). One or more treatment emergent adverse event occurred in 99% of patients during induction. The most common Grade ≥ 3 adverse events (AE) (≥10%) were neutropenia (42%), anemia (11%), and fatigue (10%).

"Pancreatic cancer remains an extremely challenging disease to treat because it is often diagnosed at the metastatic stage, and even those diagnosed with locally advanced disease typically have a poor prognosis," said Dr. Pascal Hammel, Gastroenterologist/Oncologist, Hôpital Beaujon, Clichy France. "Disease control is key in our patients with locally advanced disease, as it may lead to opportunities for additional treatment interventions, including radiotherapy, or even, in some favorable cases, surgical resection. The results from this study are encouraging, as it shows that induction therapy has the potential to help us achieve disease control in these locally advanced patients."

In this prospective, phase II trial conducted in the US, Canada and Europe, patients with protocol-defined locally advanced, unresectable pancreatic cancer received an induction regimen of up to 6 cycles of ABRAXANE + gemcitabine, followed by the investigator’s choice (IC) of either (a) continuation of the ABRAXANE + gemcitabine regimen, (b) treatment with chemoradiation, or (c) surgery. More than half of patients (57.5%, n = 61/106) completed the induction phase with ABRAXANE + gemcitabine treatment. Forty two percent (45/106) of patients did not complete induction treatment and the reasons for treatment discontinuation during induction included adverse events (n = 20), progressive disease (n = 8), protocol non-compliance (n = 5), physician decision (n = 6), death (n = 2), and other reasons (n = 4). At the time of data cut-off, 45 patients in the intent to treat cohort received IC therapy after induction: 11% (12/106) of patients continued ABRAXANE + gemcitabine per the protocol; 16% (17/106) received chemoradiation; and 15% of patients (16/106) with unresectable disease at the start of the study underwent tumor resection surgery following ABRAXANE + gemcitabine induction therapy. The LAPACT presentation also reported patient-reported quality of life findings across twenty-nine different symptom measures using the EORTC QLQ-C30 questionnaires.

Other relevant grade ≥3 TEAEs included thrombocytopenia (7.5%), peripheral sensory neuropathy (3.8%), diarrhea (3.8%), and febrile neutropenia (3.8%). AEs of any grade included: neutropenia (58.5%), fatigue (50%), anemia (47.2%), diarrhea (46.2%), thrombocytopenia (41.5%), peripheral sensory neuropathy (23.6%), and febrile neutropenia (3.8%).

"Since its approval to treat metastatic pancreatic cancer in 2013, the ABRAXANE + gemcitabine regimen has become a standard of care in first-line metastatic pancreatic cancer," said Nadim Ahmed, President, Hematology and Oncology for Celgene. "The findings from LAPACT offer insight into the potential of ABRAXANE-based treatment for locally advanced pancreatic cancer patients and it’s encouraging to see a nearly 9-month time to treatment failure in these patients treated with an ABRAXANE regimen."

ABRAXANE is not indicated for the first-line treatment of locally advanced pancreatic cancer.

ABOUT LAPACT,

LAPACT is an international, non-randomized, open-label, multi-center, phase II clinical trial conducted at 42 centers in 5 countries. The study evaluated the safety and efficacy of the investigational use of ABRAXANE in combination with gemcitabine as a first-line treatment of patients with locally advanced pancreatic cancer who were not eligible for resection surgery at trial initiation.

The trial evaluated 106 patients with locally advanced pancreatic cancer who had not received prior treatment for their pancreatic cancer and were classified as unresectable at the start of the trial. Patients were given ABRAXANE 125 mg/m2 followed by gemcitabine 1000 mg/m2 on days 1, 8 and 15 of a 28-day cycle for up to six cycles. Patients completing six cycles of treatment were given subsequent investigator-determined treatment of either: continuation of the ABRAXANE + gemcitabine regimen; chemoradiation therapy with capecitabine or gemcitabine + radiation; or surgical intervention. The median age of the patients was 65 years.

Currently, there are more than 130 studies evaluating the use of ABRAXANE in patients with pancreatic cancer in combination with more than 50 novel agents.

ABOUT ABRAXANE

ABRAXANE is indicated for the first-line treatment of patients with metastatic adenocarcinoma of the pancreas, in combination with gemcitabine.

Important Safety Information

WARNING – NEUTROPENIA

Do not administer ABRAXANE therapy to patients who have baseline neutrophil counts of less than 1500 cells/mm3. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving ABRAXANE
Note: An albumin form of paclitaxel may substantially affect a drug’s functional properties relative to those of drug in solution. DO NOT SUBSTITUTE FOR OR WITH OTHER PACLITAXEL FORMULATIONS
CONTRAINDICATIONS

Neutrophil Counts

ABRAXANE should not be used in patients who have baseline neutrophil counts of < 1500 cells/mm3
Hypersensitivity

Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with the drug
WARNINGS AND PRECAUTIONS

Hematologic Effects

Bone marrow suppression (primarily neutropenia) is dose-dependent and a dose-limiting toxicity of ABRAXANE. In clinical studies, Grade 3-4 neutropenia occurred in 47% of patients with non-small cell lung cancer (NSCLC) and 38% of patients with pancreatic cancer
Monitor for myelotoxicity by performing complete blood cell counts frequently, including prior to dosing on Days 1, 8, and 15 for NSCLC and for pancreatic cancer
Do not administer ABRAXANE to patients with baseline absolute neutrophil counts (ANC) of less than 1500 cells/mm3
In patients with adenocarcinoma of the pancreas, withhold ABRAXANE and gemcitabine if the ANC is less than 500 cells/mm3 or platelets are less than 50,000 cells/mm3 and delay initiation of the next cycle if the ANC is less than 1500 cells/mm3 or platelet count is less than 100,000 cells/mm3 on Day 1 of the cycle. Resume treatment with appropriate dose reduction if recommended
Nervous System

Sensory neuropathy is dose- and schedule-dependent
The occurrence of Grade 1 or 2 sensory neuropathy does not generally require dose modification
If ≥ Grade 3 sensory neuropathy develops, withhold ABRAXANE treatment until resolution to ≤ Grade 1 for NSCLC and pancreatic cancer followed by a dose reduction for all subsequent courses of ABRAXANE
Sepsis

Sepsis occurred in 5% of patients with or without neutropenia who received ABRAXANE in combination with gemcitabine
Biliary obstruction or presence of biliary stent were risk factors for severe or fatal sepsis
If a patient becomes febrile (regardless of ANC), initiate treatment with broad-spectrum antibiotics
For febrile neutropenia, interrupt ABRAXANE and gemcitabine until fever resolves and ANC ≥1500 cells/mm3, then resume treatment at reduced dose levels
Pneumonitis

Pneumonitis, including some cases that were fatal, occurred in 4% of patients receiving ABRAXANE in combination with gemcitabine
Monitor patients for signs and symptoms and interrupt ABRAXANE and gemcitabine during evaluation of suspected pneumonitis
Permanently discontinue treatment with ABRAXANE and gemcitabine upon making a diagnosis of pneumonitis
Hypersensitivity

Severe and sometimes fatal hypersensitivity reactions, including anaphylactic reactions, have been reported
Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with this drug
Hepatic Impairment

Because the exposure and toxicity of paclitaxel can be increased with hepatic impairment, administration of ABRAXANE in patients with hepatic impairment should be performed with caution
Patients with hepatic impairment may be at an increased risk of toxicity, particularly from myelosuppression, and should be monitored for development of profound myelosuppression
For pancreatic adenocarcinoma, ABRAXANE is not recommended for patients with moderate to severe hepatic impairment (total bilirubin > 1.5 x ULN and AST ≤10 x ULN)
Albumin (Human)

ABRAXANE contains albumin (human), a derivative of human blood
Use in Pregnancy: Pregnancy Category D

ABRAXANE can cause fetal harm when administered to a pregnant woman
If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus
Women of childbearing potential should be advised to avoid becoming pregnant while receiving ABRAXANE
Use in Men

Men should be advised not to father a child while receiving ABRAXANE
ADVERSE REACTIONS

Among the most common (≥20%) adverse reactions in the phase III study, those with a ≥5% higher incidence in the ABRAXANE/gemcitabine group compared with the gemcitabine group are neutropenia (73%, 58%), fatigue (59%, 46%), peripheral neuropathy (54%, 13%), nausea (54%, 48%), alopecia (50%, 5%), peripheral edema (46%, 30%), diarrhea (44%, 24%), pyrexia (41%, 28%), vomiting (36%, 28%), decreased appetite (36%, 26%), rash (30%, 11%), and dehydration (21%, 11%)
Of these most common adverse reactions, those with a ≥2% higher incidence of Grade 3-4 toxicity in the ABRAXANE/gemcitabine group compared with the gemcitabine group, respectively, are neutropenia (38%, 27%), fatigue (18%, 9%), peripheral neuropathy (17%, 1%), nausea (6%, 3%), diarrhea (6%, 1%), pyrexia (3%, 1%), vomiting (6%, 4%), decreased appetite (5%, 2%), and dehydration (7%, 2%)
Thrombocytopenia (all grades) was reported in 74% of patients in the ABRAXANE/gemcitabine group vs 70% of patients in the gemcitabine group
The most common serious adverse reactions of ABRAXANE (with a ≥1% higher incidence) are pyrexia (6%), dehydration (5%), pneumonia (4%), and vomiting (4%)
The most common adverse reactions resulting in permanent discontinuation of ABRAXANE were peripheral neuropathy (8%), fatigue (4%), and thrombocytopenia (2%)
The most common adverse reactions resulting in dose reduction of ABRAXANE are neutropenia (10%) and peripheral neuropathy (6%)
The most common adverse reactions leading to withholding or delay in ABRAXANE dosing are neutropenia (16%), thrombocytopenia (12%), fatigue (8%), peripheral neuropathy (15%), anemia (5%), and diarrhea (5%)
Other selected adverse reactions with a ≥5% higher incidence for all-grade toxicity in the ABRAXANE/gemcitabine group compared to the gemcitabine group, respectively, are asthenia (19%, 13%), mucositis (10%, 4%), dysgeusia (16%, 8%), headache (14%, 9%), hypokalemia (12%, 7%), cough (17%, 7%), epistaxis (15%, 3%), urinary tract infection (11%, 5%), pain in extremity (11%, 6%), arthralgia (11%, 3%), myalgia (10%, 4%), and depression (12%, 6%)
Other selected adverse reactions with a ≥2% higher incidence for Grade 3-4 toxicity in the ABRAXANE/gemcitabine group compared to the gemcitabine group are thrombocytopenia (13%, 9%), asthenia (7%, 4%), and hypokalemia (4%, 1%)
Postmarketing Experience With ABRAXANE and Other Paclitaxel Formulations

Severe and sometimes fatal hypersensitivity reactions have been reported with ABRAXANE. The use of ABRAXANE in patients previously exhibiting hypersensitivity to paclitaxel injection or human albumin has not been studied
There have been reports of congestive heart failure, left ventricular dysfunction, and atrioventricular block with ABRAXANE, primarily among individuals with underlying cardiac history or prior exposure to cardiotoxic drugs
There have been reports of extravasation of ABRAXANE. Given the possibility of extravasation, it is advisable to monitor closely the ABRAXANE infusion site for possible infiltration during drug administration
DRUG INTERACTIONS

Caution should be exercised when administering ABRAXANE concomitantly with medicines known to inhibit or induce either CYP2C8 or CYP3A4
USE IN SPECIFIC POPULATIONS

Nursing Mothers

It is not known whether paclitaxel is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother
Pediatric

The safety and effectiveness of ABRAXANE in pediatric patients have not been evaluated
Geriatric

Myelosuppression, peripheral neuropathy, and arthralgia were more frequent in patients ≥65 years of age treated with ABRAXANE and carboplatin in NSCLC
Diarrhea, decreased appetite, dehydration, and epistaxis were more frequent in patients 65 years or older compared with patients younger than 65 years old who received ABRAXANE and gemcitabine in adenocarcinoma of the pancreas
Renal Impairment

There are insufficient data to permit dosage recommendations in patients with severe renal impairment or end stage renal disease (estimated creatinine clearance < 30 mL/min)
DOSAGE AND ADMINISTRATION

Do not administer ABRAXANE to any patient with total bilirubin greater than 5 x ULN or AST greater than 10 x ULN
Do not administer ABRAXANE to patients with metastatic adenocarcinoma of the pancreas who have moderate to severe hepatic impairment
Dose reductions or discontinuation may be needed based on severe hematologic, neurologic, cutaneous, or gastrointestinal toxicity
Monitor patients closely
Please see full Prescribing Information, including Boxed WARNING.

On January 18, 2018 Kite, a Gilead Company (Nasdaq: GILD), reported it has entered into a clinical trial collaboration with Pfizer, Inc. to evaluate the safety and efficacy of the investigational combination of Yescarta (axicabtagene ciloleucel) and Pfizer’s utomilumab, a fully humanized 4-1BB agonist monoclonal antibody, in patients with refractory large B-cell lymphoma (Press release, Kite Pharma, JAN 18, 2018, View Source;p=irol-newsArticle&ID=2327256 [SID1234523300]). A multi-center Phase 1/2 study sponsored by Kite is expected to begin in 2018. The results of this study will be used to evaluate options for further development of this combination, or similar combinations between Kite’s engineered T cell products and utomilumab.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Yescarta is the first chimeric antigen receptor T (CAR T) cell therapy to be indicated for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including DLBCL not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma and DLBCL arising from follicular lymphoma. Yescarta is not indicated for patients with primary central nervous system lymphoma.

Utomilumab, also known as PF-05082566, is an investigational 4-1BB agonist that has been shown in preclinical models to enhance T cell mediated immune responses. Pfizer is currently investigating utomilumab in both hematologic cancers and solid tumors as a single agent and in combination with other anti-cancer therapies. Evidence also suggests that 4-1BB, a costimulatory protein expressed on activated T cells, is upregulated upon exposure to CD19-expressing tumor cells. Utomilumab could potentially enhance T cell proliferation and activity by augmenting the CD28 costimulatory domain of Yescarta with exogenous 4-1BB signaling.

"Kite is committed to realizing the full potential of Yescarta and other cell therapy technologies across a range of cancers," said David Chang, MD, PhD, Worldwide Head of Research and Development and Chief Medical Officer at Kite. "We are pleased to collaborate with Pfizer on this study with utomilumab, which adds to the growing number of combination approaches we are exploring with Yescarta for patients living with lymphoma."

The combination of Yescarta and utomilumab is investigational and has not been proven safe and effective.

U.S. Important Safety Information for Yescarta

BOXED WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITIES

Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving Yescarta. Do not administer Yescarta to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving Yescarta, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities after treatment with Yescarta. Provide supportive care and/or corticosteroids as needed.
Yescarta is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta REMS.

Cytokine Release Syndrome (CRS)

CRS, including fatal or life-threatening reactions, occurred following treatment with Yescarta. In Study 1, CRS occurred in 94% (101/108) of patients receiving Yescarta, including ≥ Grade 3 (Lee grading system) CRS in 13% (14/108) of patients. Among patients who died after receiving Yescarta, four had ongoing CRS events at the time of death. The median time to onset was 2 days (range: 1 to 12 days) and the median duration of CRS was 7 days (range: 2 to 58 days). Key manifestations of CRS include fever (78%), hypotension (41%), tachycardia (28%), hypoxia (22%), and chills (20%). Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).

Ensure that 2 doses of tocilizumab are available prior to infusion of Yescarta. Monitor patients at least daily for 7 days at the certified healthcare facility following infusion for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for 4 weeks after infusion. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab or tocilizumab and corticosteroids as indicated.

Neurologic Toxicities

Neurologic toxicities, that were fatal or life-threatening, occurred following treatment with Yescarta. Neurologic toxicities occurred in 87% of patients. Ninety-eight percent of all neurologic toxicities occurred within the first 8 weeks of Yescarta infusion, with a median time to onset of 4 days (range: 1 to 43 days). The median duration of neurologic toxicities was 17 days. Grade 3 or higher neurologic toxicities occurred in 31% of patients.

The most common neurologic toxicities included encephalopathy (57%), headache (44%), tremor (31%), dizziness (21%), aphasia (18%), delirium (17%), insomnia (9%) and anxiety (9%). Prolonged encephalopathy lasting up to 173 days was noted. Serious events including leukoencephalopathy and seizures occurred with Yescarta. Fatal and serious cases of cerebral edema have occurred in patients treated with Yescarta.

Monitor patients at least daily for 7 days at the certified healthcare facility following infusion for signs and symptoms of neurologic toxicities. Monitor patients for signs or symptoms of neurologic toxicities for 4 weeks after infusion and treat promptly.

Yescarta REMS

Because of the risk of CRS and neurologic toxicities, Yescarta is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta REMS. The required components of the Yescarta REMS are:

Healthcare facilities that dispense and administer Yescarta must be enrolled and comply with the REMS requirements. Certified healthcare facilities must have on-site, immediate access to tocilizumab, and ensure that a minimum of two doses of tocilizumab are available for each patient for infusion within 2 hours after Yescarta infusion, if needed for treatment of CRS.
Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense or administer Yescarta are trained about the management of CRS and neurologic toxicities.

Further information is available at www.YescartaREMS.com or 1-844-454-KITE (5483).

Hypersensitivity Reactions

Allergic reactions may occur with the infusion of Yescarta. Serious hypersensitivity reactions including anaphylaxis, may be due to dimethyl sulfoxide (DMSO) or residual gentamicin in Yescarta.

Serious Infections

Severe or life-threatening infections occurred in patients after Yescarta infusion. In Study 1, infections (all grades) occurred in 38% of patients. Grade 3 or higher infections occurred in 23% of patients. Grade 3 or higher infections with an unspecified pathogen occurred in 16% of patients, bacterial infections in 9%, and viral infections in 4%. Yescarta should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after Yescarta infusion and treat appropriately. Administer prophylactic anti-microbials according to local guidelines.

Febrile neutropenia was observed in 36% of patients after Yescarta infusion and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids and other supportive care as medically indicated.

Viral Reactivation

Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, can occur in patients treated with drugs directed against B cells. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing.

Prolonged Cytopenias

Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and Yescarta infusion. In Study 1, Grade 3 or higher cytopenias not resolved by Day 30 following Yescarta infusion occurred in (28%) of patients and included thrombocytopenia (18%), neutropenia (15%), and anemia (3%). Monitor blood counts after Yescarta infusion.

Hypogammaglobulinemia

B-cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with Yescarta. In Study 1, hypogammaglobulinemia occurred in 15% of patients. Monitor immunoglobulin levels after treatment with Yescarta and manage using infection precautions, antibiotic prophylaxis and immunoglobulin replacement.

The safety of immunization with live viral vaccines during or following Yescarta treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during Yescarta treatment, and until immune recovery following treatment with Yescarta.

Secondary Malignancies

Patients treated with Yescarta may develop secondary malignancies. Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs, contact Kite at 1-844-454-KITE (5483) to obtain instructions on patient samples to collect for testing.

Effects on Ability to Drive and Use Machines

Due to the potential for neurologic events, including altered mental status or seizures, patients receiving Yescarta are at risk for altered or decreased consciousness or coordination in the 8 weeks following Yescarta infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.

Adverse Reactions

The most common adverse reactions (incidence ≥ 20%) include CRS, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, decreased appetite, chills, diarrhea, febrile neutropenia, infections-pathogen unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness, constipation, and cardiac arrhythmias. Serious adverse reactions occurred in 52% of patients. The most common serious adverse reactions (> 2%) include encephalopathy, fever, lung infection, febrile neutropenia, cardiac arrhythmia, cardiac failure, urinary tract infection, renal insufficiency, aphasia, cardiac arrest, Clostridium difficile infection, delirium, hypotension, and hypoxia.

The most common (≥ 10%) Grade 3 or higher reactions include febrile neutropenia, fever, CRS, encephalopathy, infections-pathogen unspecified, hypotension, hypoxia and lung infections.

U.S. Indication for Yescarta

Yescarta is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.

Limitation of Use: Yescarta is not indicated for the treatment of patients with primary central nervous system lymphoma.

On January 18, 2018 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it has obtained approval of its humanized anti-PD-L1 (Programmed Death Ligand-1) monoclonal antibody, "TECENTRIQ Intravenous Infusion 1200mg" (generic name: atezolizumab [recombinant]) from the Ministry of Health, Labour and Welfare (MHLW) for the treatment of "unresectable advanced or recurrent non-small cell lung cancer (NSCLC) (Press release, Chugai, JAN 18, 2018, View Source [SID1234523305])."

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"This is the first approval for TECENTRIQ in Japan, and it also represents the first step for Chugai to provide cancer immunotherapy," said Chugai’s President & COO, Tatsuro Kosaka. "We have been preparing for the new launch to provide TECENTRIQ for all patients as early as possible, and will take every measures to deliver the information needed to promote its appropriate use."

TECENTRIQ is a PD-L1 targeting monoclonal antibody created by Genetench, a member of the Roche Group. PD-L1 is a protein expressed on tumor and tumor-infiltrating immune cells that blocks T cell activity by binding with PD-1 and B7.1 receptors on T cell surface. By inhibiting PD-L1, TECENTRIQ may enable the activation of T cells and boost immune response against cancer cells.

TECENTRIQ is already approved in the European Union, United States and more than 50 countries for people with previously treated metastatic NSCLC and for people with locally advanced or metastatic urothelial cancer who are not eligible for cisplatin chemotherapy, or who have had disease progression during or following platinum-containing therapy. In Japan, Chugai has been conducting seven clinical studies in the NSCLC setting to evaluate TECENTRIQ alone or in combination with other drugs. In addition to NSCLC studies, several phase III studies are ongoing for small-cell lung cancer, urotherial carcinoma, breast cancer, renal cell carcinoma, ovarian cancer and prostate cancer.

In Japan, the annual prevalence of lung cancer is estimated to be approximately 134,000 in 2015 (male: 91,000, female: 43,000). The annual mortality of lung cancer, the leading cause of cancer deaths in Japan, is approximately 77,000 (male: 55,000, female: 22,000; predicted figure for 2015).*

As a top pharmaceutical company in the field of oncology in Japan, Chugai is committed to contribute to patients with lung cancers and medical professionals by offering TECENTRIQ as a new treatment option.

About conditions for approval of TECENTRIQ
A drug use surveillance of all patients who receive TECENTRIQ must be conducted until the data on a given number of patients is accumulated.

About the drug use surveillance of TECENTRIQ (All-case registration surveillance)
The all-case registration surveillance is scheduled to collect the data of 1,000 patients who receive TECENTRIQ treatment. Once data for the first 1,000 cases is accumulated, the data will be reviewed to determine whether a new surveillance or further safety measures should be conducted. Results of the surveillance will be reported to the regulatory authorities, and the data shall be announced at future scientific meetings.

Note: The description of INDICATIONS in the Japanese package insert
The following description is noted as in the INDICATIONS:

Efficacy and safety of TECENTRIQ in chemotherapy-naïve patients have not been established.
Efficacy and safety have not been established for postoperative adjuvant chemotherapy with TECENTRIQ.
Eligible patients should be selected after closely reading the CLINICAL STUDIES section, which provides information such as the prior treatment history of patients in the clinical studies, in order to gain a thorough understanding of the efficacy and safety of TECENTRIQ.

On January 18, 2018 Alexion Pharmaceuticals, Inc. (Nasdaq: ALXN) reported that the Company will report its financial results for the fourth quarter and full year ended December 31, 2017 on Thursday, February 8, 2018 before the US financial markets open (Press release, Alexion, JAN 18, 2018, View Source [SID1234523288]). Following the release of the financial results, Alexion management will conduct a conference call and audio webcast on Thursday, February 8, 2018, at 10:00 a.m. Eastern Time (ET).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

To participate in this conference call, dial 800-239-9838 (USA) or 323-794-2551 (International), passcode 7453141 shortly before 10:00 a.m. ET. A replay of the call will be available from 1:00 p.m. ET through a limited time thereafter. The replay number is 888-203-1112 (USA) or 719-457-0820 (International), passcode 7453141. The audio webcast can be accessed on the Investor page of View Source

On January 18, 2018 Seattle Genetics, Inc. (Nasdaq: SGEN) reported that it will report its fourth quarter and year 2017 financial results on Tuesday, February 6, 2018 after the close of financial markets. Following the results announcement, company management will host a conference call and webcast discussion of the results and provide a general corporate update (Press release, Seattle Genetics, JAN 18, 2018, View Source;p=RssLanding&cat=news&id=2327230 [SID1234523280]). Access to the event can be obtained as follows:

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

LIVE access on Tuesday, February 6, 2018
1:30 p.m. Pacific Time / 4:30 p.m. Eastern Time

Telephone 888-778-9065 (domestic) or 719-325-2452 (international); conference ID 9278036
Webcast available at www.seattlegenetics.com in the Investors section
REPLAY access

Telephone replay will be available beginning at approximately 4:30 p.m. PT on Tuesday, February 6, 2018 through 5:00 p.m. PT on Friday, February 9, 2018 by calling 888-203-1112 (domestic) or 719-457-0820 (international); conference ID 9278036
Webcast replay will be available on the Seattle Genetics website at www.seattlegenetics.com in the Investors section