On December 8, 2015 Pfizer Inc. reported the first-ever recipients of the Advancing Science through Pfizer Investigator Research Exchange (ASPIRE) Breast Cancer Research Awards (Press release, Pfizer, DEC 8, 2015, View Source [SID:1234508494]). Five grants totaling more than $4 million in funding were awarded to support clinical research projects investigating IBRANCE (palbociclib), an oral, first-in-class inhibitor of cyclin-dependent kinases (CDKs) 4 and 6, in advanced breast cancer for 2015. Simultaneously, the company announced that it will award up to $4 million in new grants through the ASPIRE Breast Cancer Research Awards Program in 2016.

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"We are excited to support these five investigator-led studies, which we believe will contribute important new information to our body of knowledge about the role IBRANCE plays in the treatment and clinical management of advanced breast cancer," said Dr. Julia Perkins Smith, senior medical director, U.S. Breast Cancer Lead, Pfizer Oncology. "At the same time, we are looking forward to continuing the program in 2016 and further supporting investigators’ efforts in this disease area, where there is a substantial need for research that may lead to new options and improved care for metastatic breast cancer patients. Supporting the scientific and clinical exploration of our medicines both within and outside our walls is critical to our ability to make a meaningful impact on patients’ lives."

The ASPIRE Breast Cancer Research Awards Program is an extension of ASPIRE, Pfizer’s competitive grants program. Recipients were selected through a competitive application process overseen by an independent review panel of breast cancer experts. The following five investigators and studies have been awarded grants through the program to date:

Sara Tolaney, MD, MPH, Dana-Farber Cancer Institute – A Phase Ib/IIa Study of Palbociclib in Combination With Everolimus and Exemestane in Postmenopausal Women With Estrogen Receptor Positive and HER2 Negative Metastatic Breast Cancer
Ewa Mrozek, MD, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute – A Phase II Trial of Primary Endocrine Therapy With Combination of Fulvestrant and Palbociclib in Elderly Patients With Hormone Responsive Breast Cancer Who Have Inoperable Tumor or Operable Tumor but Cannot Undergo Surgery Due to Frailty

Oana Danciu, MD, University of Illinois at Chicago – A Single Arm Phase II Study of Palbociclib in Combination With Tamoxifen as First Line Therapy for Metastatic Hormone Receptor Positive Breast Cancer

Cesar Augusto Santa-Maria, MD, Northwestern University – A Single Arm Phase II Study of Palbociclib in Patients With Metastatic HER2-positive or Triple Negative Breast Cancer With Brain Metastasis

Filipa Lynce, MD, Lombardi Comprehensive Cancer Center at Georgetown University Medical Center – A Phase II Safety Study of Palbociclib in Combination With Letrozole in African American Women with Hormone Receptor Positive HER2 Negative Advanced Breast Cancer

For the new 2016 grants, investigators are encouraged to submit for consideration proposals for innovative research in several areas. Some areas of research interest include:

Improving the medical knowledge of palbociclib in the treatment of advanced breast cancer through exploring the safety and efficacy of novel combinations

Optimizing clinical management during palbociclib treatment that addresses or improves patient compliance and convenience and/or patient reported outcomes

Exploring biomarkers relevant to palbociclib in breast cancer

For more information about the 2016 ASPIRE Breast Cancer Research Awards Program and specifics regarding eligible areas of research, please visit www.aspireresearch.org (link is external). The proposal submission period ends March 31, 2016.

About IBRANCE (palbociclib)

IBRANCE is an oral, first-in-class inhibitor of cyclin-dependent kinases (CDKs) 4 and 6. CDKs 4 and 6 are key regulators of the cell cycle that trigger cellular progression.1,2

IBRANCE is approved by the FDA for use in combination with letrozole as a treatment for postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+, HER2-) advanced breast cancer as initial endocrine-based therapy for their metastatic disease.3 The effectiveness of IBRANCE in these patients is based on a study that measured progression-free survival.3 Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. The confirmatory Phase 3 trial, PALOMA-2, is fully enrolled. The full prescribing information for IBRANCE can be found at www.IBRANCE.com (link is external).

IBRANCE has also received regulatory approval in Albania, Chile and Macau. In the European Union, the Marketing Authorization Application for IBRANCE, which is based on results from the PALOMA-1 and PALOMA-3 trials, is currently under review with the European Marketing Agency.

Important IBRANCE (palbociclib) Safety Information

Neutropenia: Neutropenia is frequently reported with IBRANCE therapy. In the randomized phase II study, Grade 3 (57%) or 4 (5%) decreased neutrophil counts were reported in patients receiving IBRANCE plus letrozole. Febrile neutropenia can occur.

Monitor complete blood count prior to starting IBRANCE and at the beginning of each cycle, as well as Day 14 of the first two cycles, and as clinically indicated. For patients who experience Grade 3 neutropenia, consider repeating the complete blood count monitoring 1 week later. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia.

Infections: Infections have been reported at a higher rate in patients treated with IBRANCE plus letrozole (55%) compared with letrozole alone (34%). Grade 3 or 4 infections occurred in 5% of patients treated with IBRANCE plus letrozole vs no patients treated with letrozole alone. Monitor patients for signs and symptoms of infection and treat as medically appropriate.

Pulmonary embolism (PE): PE has been reported at a higher rate in patients treated with IBRANCE plus letrozole (5%) compared with no cases in patients treated with letrozole alone. Monitor patients for signs and symptoms of PE and treat as medically appropriate.

Pregnancy and lactation: Based on the mechanism of action, IBRANCE can cause fetal harm. Advise females with reproductive potential to use effective contraception during therapy with IBRANCE and for at least 2 weeks after the last dose. Advise females to contact their healthcare provider if they become pregnant or if pregnancy is suspected during treatment with IBRANCE. Advise women not to breastfeed while on IBRANCE therapy because of the potential for serious adverse reactions in nursing infants from IBRANCE.

Additional hematologic abnormalities: Decreases in hemoglobin (83% vs 40%), leukocytes (95% vs 26%), lymphocytes (81% vs 35%), and platelets (61% vs 16%) occurred at a higher rate in patients treated with IBRANCE plus letrozole vs letrozole alone.

Adverse reactions: The most common all causality adverse reactions (≥10%) of any grade reported in patients treated with IBRANCE plus letrozole vs letrozole alone in the phase II study included neutropenia (75% vs 5%), leukopenia (43% vs 3%), fatigue (41% vs 23%), anemia (35% vs 7%), upper respiratory infection (31% vs 18%), nausea (25% vs 13%), stomatitis (25% vs 7%), alopecia (22% vs 3%), diarrhea (21% vs 10%), thrombocytopenia (17% vs 1%), decreased appetite (16% vs 7%), vomiting (15% vs 4%), asthenia (13% vs 4%), peripheral neuropathy (13% vs 5%), and epistaxis (11% vs 1%).

Grade 3/4 adverse reactions reported (≥10%) occurring at a higher incidence in the IBRANCE plus letrozole vs letrozole alone group include neutropenia (54% vs 1%) and leukopenia (19% vs 0%). The most frequently reported serious adverse events in patients receiving IBRANCE were pulmonary embolism (4%) and diarrhea (2%).

General dosing information: The recommended dose of IBRANCE is 125 mg taken orally once daily for 21 days followed by 7 days off treatment in 28-day cycles. IBRANCE should be taken with food and in combination with letrozole 2.5 mg once daily continuously.

Patients should be encouraged to take their dose at approximately the same time each day.

Capsules should be swallowed whole. No capsule should be ingested if it is broken, cracked, or otherwise not intact. If a patient vomits or misses a dose, an additional dose should not be taken that day. The next prescribed dose should be taken at the usual time.

Management of some adverse reactions may require temporary dose interruption/delay and/or dose reduction, or permanent discontinuation. Dose modification of IBRANCE is recommended based on individual safety and tolerability.

Drug interactions: Avoid concurrent use of strong CYP3A inhibitors. If patients must be administered a strong CYP3A inhibitor, reduce the IBRANCE dose to 75 mg/day. If the strong inhibitor is discontinued, increase the IBRANCE dose (after 3-5 half-lives of the inhibitor) to the dose used prior to the initiation of the strong CYP3A inhibitor. Grapefruit or grapefruit juice may increase plasma concentrations of IBRANCE and should be avoided.

Avoid concomitant use of strong and moderate CYP3A inducers. The dose of the sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced as IBRANCE may increase their exposure.

Hepatic and renal impairment: IBRANCE has not been studied in patients with moderate to severe hepatic impairment or in patients with severe renal impairment (CrCl <30 mL/min).

On December 8, 2015 OncoSec Medical Incorporated ("OncoSec") (NASDAQ: ONCS), a company developing DNA-based intratumoral cancer immunotherapies, reported financial results for the first quarter of fiscal year ended July 31, 2016 (Press release, OncoSec Medical, DEC 8, 2015, View Source [SID:1234508493]).

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FINANCIAL RESULTS
For the first quarter of fiscal 2016, OncoSec reported a net loss of $7.0 million, or $0.47 per share, compared to a net loss of $4.1 million, or $0.33 per share, for the same period last year. The net loss includes non-cash items such as stock compensation expense and depreciation. The increase in net loss for the quarter-ended October 31, 2015, resulted primarily from (i) additional outside services costs to support our development of next-generation device prototypes and clinical studies, (ii) additional reagent and lab supply costs to support discovery research, (iii) incremental legal and audit fees and (iv) an increase in non-cash stock-based compensation expense primarily related to our increased headcount. There were no revenues for the quarter-ended October 31, 2015 or October 31, 2014.

Research and development expenses were $3.7 million for the first quarter of fiscal 2016, compared to $2.5 million for the same period in fiscal 2015. General and administrative expenses were $3.4 million for the first quarter of fiscal 2016, compared to $1.6 million for the same period in fiscal 2015.

At October 31, 2015, OncoSec had $26.9 million in cash and cash equivalents, as compared to $32.0 million of cash and cash equivalents at October 31, 2014. OncoSec expects these funds to be sufficient to allow the Company to continue to operate its business for at least the next 12 months.

On December 8, 2015 Oncolytics Biotech Inc. ("Oncolytics") (TSX:ONC) (OTCQX:ONCYF) (FRA:ONY) reported that Dr. D.W. Sborov and colleagues made a poster presentation at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Oncolytics Biotech, DEC 8, 2015, View Source [SID:1234508492]). The poster presentation, titled "REOLYSIN Combined with Carfilzomib for Treatment of Relapsed Multiple Myeloma Patients," discloses updated findings from a pilot study (NCI-9603) in patients with relapsed or refractory multiple myeloma treated using the combination of carfilzomib and REOLYSIN. The ASH (Free ASH Whitepaper) Annual Meeting runs from December 5th to 8th in Orlando, FL.

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Highlights of the data presented include:

All seven patients treated at the full clinical dose had a clinical response. Patients treated at the full clinical dose (dose level 1) had a deeper and more prolonged response than those treated at dose level minus 1. Of the 12 total patients treated, 11 had a decrease in dominant monoclonal protein during treatment (used to measure clinical response), including all seven patients treated at the full clinical dose;

The combination of carfilzomib and REOLYSIN produced a significant (p=0.005) increase in caspase-3, a marker associated with apoptotic (programmed) cell death, but to a higher degree in those patients treated at dose level 1; and

The treatment combination was associated with an increased infiltration of CD8+ T-cells and the significant (p=0.005) upregulation of PD-L1, suggesting that the addition of a PD-1 or PD-L1 inhibitor may further optimize the treatment regimen.

"These findings are compelling as we continue to see a strong clinical benefit rate in this difficult to treat cancer, and clear evidence of a dose response, with patients at the higher dosing level seeing improved outcomes. We plan on testing higher dosage levels to determine the extent of this improvement," said Dr. Matt Coffey, Chief Operating Officer of Oncolytics. "We recently announced a second study in multiple myeloma examining REOLYSIN together with bortezomib, with the goal of identifying the best standard of care combination to advance into later stage clinical testing."

The investigators noted that this is the first time a REOLYSIN-based combination has been tested in relapsed multiple myeloma patients. A previous single-agent study conducted by the collaborators in this patient population showed that REOLYSIN was well tolerated. The collaborators and others were noted to have conducted preclinical investigations that demonstrated that the combination of REOLYSIN and carfilzomib synergistically increased the killing of multiple myeloma cells. This provided the clinical rationale for this study.

"Based on these evolving data and input received from key opinion leaders, we believe multiple myeloma to be a compelling registration target," said Dr. Brad Thompson, President and CEO of Oncolytics. "We intend to discuss the design of a potential registration study with regulatory agencies."

NCI-9603 is a U.S. National Cancer Institute sponsored single-arm, open-label study of intravenously administered REOLYSIN with dexamethasone and carfilzomib to patients with relapsed or refractory multiple myeloma. Patients receive treatment on days 1, 2, 8, 9, 15 and 16 of a 28-day cycle, to be repeated in the absence of disease progression or unacceptable toxicity. Approximately 12 patients will be enrolled in the study. The primary outcome measures include reovirus replication, safety, and tolerability. Secondary outcome measures include examining objective response, duration of response, clinical benefit, progression-free survival, and time to progression. Other outcome measures will include immunologic correlative markers.

A copy of the poster will be available on the Oncolytics website at: View Source

About Multiple Myeloma
Multiple Myeloma is a cancer of the plasma cells and the second most common hematological malignancy. The American Cancer Society estimates there will be 26,850 new cases diagnosed in the United States and 11,240 deaths from the disease in 2015.

On December 8, 2015 Cerus Corporation (NASDAQ:CERS), a biomedical products company focused on improving blood transfusion safety, reported that Smilow Cancer Hospital at Yale-New Haven has enrolled the first patient in the Phase IV INTERCEPT Platelets Entering Routine Use (PIPER) study, a prospective, open-label, non-inferiority, post-marketing surveillance study (Press release, Cerus, DEC 8, 2015, View Source [SID:1234508486]). The PIPER study is expected to enroll approximately 3,000 patients at a targeted 15 – 20 U.S. hospitals.

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"Smilow Cancer Hospital at Yale New-Haven, as a leading U.S. cancer hospital, is dedicated to providing our patients with the best care available," said Edward Snyder, MD, Professor of Laboratory Medicine and Director of Transfusion/Apheresis/Tissue Implantation Services. "We recognize the risks faced by these immunosuppressed patients and believe that our participation in the PIPER study will allow us to learn more about platelet transfusions and pulmonary events in this seriously ill patient population, as well as to provide the highest level of transfusion safety."

Yale Cancer Center is one of 45 National Cancer Institute designated comprehensive cancer centers in the U.S., and is Connecticut’s largest cancer care provider, participating in over 150 cancer-focused clinical trials. The Yale team is led by Eric Gehrie, MD and Jeanne Hendrickson, MD in addition to Dr. Snyder. "The Yale team looks forward to our collaboration with Cerus on this Phase IV study," commented Dr. Snyder.

The PIPER study will monitor the transfusion of conventional and INTERCEPT-treated platelets in hematology/oncology patients, including those undergoing hematopoietic stem cell transplant, who are expected to require one or more platelet component transfusions. PIPER will evaluate the incidence of severe pulmonary adverse events requiring assisted mechanical ventilation, a clinical concern in transfusion medicine as it relates to repeated platelet transfusions in patient populations at risk for lung injury.
"We appreciate Smilow Cancer Hospital’s leadership in this study," said Dr. Laurence Corash, Cerus’ Chief Scientific Officer. "PIPER’s unique design will allow Cerus to expand our large portfolio of safety data for routine use of INTERCEPT-treated platelets."
"There has been a strong level of interest in participation in PIPER across leading U.S. cancer hospitals. Physicians recognize the continued infectious risks associated with platelet transfusions, as well as the opportunity to reduce these risks afforded by pathogen reduced platelets," said William ‘Obi’ Greenman, Cerus’ President and Chief Executive Officer. "Patient safety is of utmost importance for hematology/oncology patients enrolling in PIPER."

The INTERCEPT Blood System for platelets and plasma has been used in European blood centers for over a decade. The INTERCEPT Blood System received FDA approval in December 2014. The INTERCEPT Blood System leverages the understanding that platelets and plasma do not require functional DNA or RNA, as opposed to pathogens and donor white blood cells. Pathogen reduction with the INTERCEPT Blood System is designed to block the replication process so that harmful viruses, bacteria, and parasites can no longer replicate and cause disease.

ABOUT THE PIPER STUDY
PIPER is a prospective, open-label surveillance study designed to evaluate the transfusion of conventional and INTERCEPT-treated platelets in hematology/oncology patients, including those undergoing hematopoietic stem cell transplant, who are expected to require one or more platelet component transfusions. INTERCEPT-treated platelets will not require gamma irradiation or bacterial detection. PIPER will evaluate the frequency of assisted mechanical ventilation required to treat severe pulmonary complications, a common clinical concern in transfusion medicine as it relates to repeated platelet transfusions in patient populations at risk for pulmonary complications, such as hematology/oncology patients. The primary endpoint will be assessed by and independent pulmonary expert adjudication panel.

The PIPER Phase IV study is currently open and recruiting hospital participants. For more information, please visit View Source or www.clinicaltrials.gov. To become a study site or for more information about participating, please contact Cerus Corporation via e-mail at [email protected].

ABOUT THE INTERCEPT BLOOD SYSTEM FOR PLATELETS
The INTERCEPT Blood System for platelets is designed for the ex vivo preparation and storage of whole blood-derived and apheresis platelets. The device uses amotosalen HCl (a photoactive compound) and long-wavelength ultraviolet (UVA) illumination to photochemically treat platelet components. It has been approved in the U.S. since 2014 and in Europe since 2002, and is currently used in over 100 blood centers in 20 countries.

The safety and efficacy of INTERCEPT-processed platelets has been evaluated in 10 controlled clinical studies, with over 800 study subjects. Routine use of INTERCEPT-processed platelets has been monitored in over 4,000 patients in active hemovigilance studies conducted by Cerus in Europe, and additionally through national hemovigilance reporting systems in France (since 2009) and Switzerland (since 2010). For U.S. product information, see View Source

On December 8, 2015 Gilead Sciences, Inc. (Nasdaq: GILD) reported results from a prespecified interim analysis of a Phase 3 study (Study 115) evaluating Zydelig (idelalisib) in combination with bendamustine and rituximab (BR) for patients with previously treated CLL (Press release, Gilead Sciences, DEC 8, 2015, View Source;p=irol-newsArticle&ID=2120907 [SID:1234508483]). The analysis found a 67 percent reduction in the risk of disease progression or death (progression-free survival, PFS) in patients receiving Zydelig plus BR compared to BR alone (hazard ratio (HR) = 0.33; 95 percent CI: 0.24, 0.45; p<0.0001). Additionally, all secondary endpoints, including overall survival (OS), achieved statistical significance in this interim analysis. Detailed results were presented today during the late-breaking abstracts session at the Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in Orlando, Florida (#LBA-5).

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"These new findings add to the role of idelalisib-containing regimens for the treatment of relapsed CLL," said Andrew D. Zelenetz, MD, PhD, Medical Oncologist and Vice Chair, Medical Informatics, Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center. "In this Phase 3 study, adding idelalisib to BR provided not only statistically significant but clinically meaningful improvements in progression-free and overall survival compared to BR, a current standard of care in relapsed/refractory CLL. Further, idelalisib treatment also benefitted patients with genetic factors associated with a poorer prognosis."

Zydelig is approved in the United States in combination with rituximab for patients with relapsed CLL for whom rituximab alone would be considered appropriate therapy due to comorbidities. Based on the Study 115 results, Gilead plans to submit supplemental regulatory filings in the U.S. and Europe early next year.

Study 115 enrolled 416 adult patients with previously treated CLL whose disease had progressed less than 36 months following completion of prior therapy, and was not refractory to bendamustine. Eligible patients were randomized (1:1) to receive six cycles of BR over 24 weeks with either Zydelig 150 mg or placebo taken orally twice daily until disease progression or unacceptable toxicity. In November, the trial was unblinded following the recommendation of an independent Data Monitoring Committee.

The primary endpoint was PFS, defined as the time from randomization to definitive disease progression or death, as assessed by an independent review committee. Median PFS for patients receiving Zydelig plus BR was 23.1 months compared to 11.1 months for patients receiving placebo plus BR. Among patients with a 17p deletion or TP53 mutation (Zydelig plus BR: n=69; placebo plus BR: n=68), genetic abnormalities that have been linked to poor prognosis, there was a 50 percent reduction in the risk of disease progression or death (HR=0.50, 95 percent CI: 0.32, 0.77).

The study also found a statistically significant benefit in OS, with a 45 percent reduction in the risk of death among patients receiving Zydelig plus BR compared to those receiving BR alone (HR=0.55; 95 percent CI: 0.36, 0.86; p=0.008). Median OS has not been reached in either arm. The overall response rate (ORR) was 68 percent in the Zydelig arm and 45 percent for the control arm.

Grade ≥3 adverse events for the Zydelig plus BR and placebo plus BR arms, respectively, included neutropenia (60 versus 46 percent), febrile neutropenia (20 versus 6 percent) and diarrhea (7 versus 2 percent). Grade ≥3 elevations in ALT and AST occurred in 21 and 16 percent, respectively, of patients receiving Zydelig plus BR compared to 3 percent and 3 percent in patients receiving BR alone; see below for Important Safety Information, including BOXED WARNING.

Zydelig in combination with bendamustine and rituximab is an investigational regimen and its safety and efficacy have not been established.

About Zydelig (idelalisib)

Zydelig is an oral inhibitor of phosphoinositide 3-kinase (PI3K) delta, a protein that plays a role in the activation, proliferation and viability of B cells, a critical component of the immune system. PI3K delta signaling is active in many B-cell leukemias and lymphomas, and by inhibiting the protein, Zydelig blocks several cellular signaling pathways that drive B-cell viability.

Important U.S. Safety Information

BOXED WARNING: FATAL AND SERIOUS TOXICITIES: HEPATIC, SEVERE DIARRHEA, COLITIS, PNEUMONITIS, AND INTESTINAL PERFORATION

Fatal and/or serious hepatotoxicity occurred in 14 percent of Zydelig-treated patients. Monitor hepatic function prior to and during treatment. Interrupt and then reduce or discontinue Zydelig as recommended.

Fatal and/or serious and severe diarrhea or colitis occurred in 14 percent of Zydelig-treated patients. Monitor for the development of severe diarrhea or colitis. Interrupt and then reduce or discontinue Zydelig as recommended.

Fatal and serious pneumonitis can occur. Monitor for pulmonary symptoms and bilateral interstitial infiltrates. Interrupt or discontinue Zydelig as recommended.

Fatal and serious intestinal perforation can occur in Zydelig-treated patients. Discontinue Zydelig for intestinal perforation.

Contraindications

History of serious allergic reactions, including anaphylaxis and toxic epidermal necrolysis (TEN).
Warnings and Precautions

Hepatotoxicity: Findings were generally observed within the first 12 weeks of treatment and reversed with dose interruption. Upon rechallenge at a lower dose, ALT/AST elevations recurred in 26 percent of patients. In all patients, monitor ALT/AST every 2 weeks for the first 3 months, every 4 weeks for the next 3 months, and every 1 to 3 months thereafter. If ALT/AST is >3x upper limit of normal (ULN), monitor for liver toxicity weekly. If ALT/AST is >5x ULN, withhold Zydelig and monitor ALT/AST and total bilirubin weekly until resolved. Discontinue Zydelig for recurrent hepatotoxicity. Avoid concurrent use with other hepatotoxic drugs.

Severe diarrhea or colitis: Grade 3+ diarrhea can occur at any time and responds poorly to antimotility agents. Avoid concurrent use with other drugs that cause diarrhea.

Pneumonitis: Evaluate for pneumonitis in patients presenting with pulmonary symptoms such as cough, dyspnea, hypoxia, interstitial infiltrates on radiologic exam, or oxygen saturation decline by ≥5 percent.

Intestinal perforation: Advise patients to promptly report any new or worsening abdominal pain, chills, fever, nausea, or vomiting.
Severe cutaneous reactions: One case of TEN occurred in a study of Zydelig in combination with rituximab and bendamustine. Other severe or life-threatening (Grade ≥3) cutaneous reactions have been reported. Monitor patients for the development of severe cutaneous reactions and discontinue Zydelig if a reaction occurs.

Anaphylaxis: Serious allergic reactions including anaphylaxis have been reported. Discontinue Zydelig permanently and institute appropriate supportive measures if a reaction occurs.

Neutropenia: Treatment-emergent Grade 3-4 neutropenia occurred in 31 percent of Zydelig-treated patients in clinical trials. In all patients, monitor blood counts ≥every 2 weeks for the first 3 months. In patients with neutrophil counts <1.0 Gi/L, monitor weekly.

Embryo-fetal toxicity: Zydelig may cause fetal harm. Women who are or become pregnant while taking Zydelig should be apprised of the potential hazard to the fetus. Advise women to avoid pregnancy while taking Zydelig and to use effective contraception during and at least 1 month after treatment with Zydelig.

Adverse Reactions

Most common adverse reactions (incidence ≥20 percent; all grades) in clinical studies, when used alone or in combination with rituximab, were diarrhea, pyrexia, fatigue, nausea, cough, pneumonia, abdominal pain, chills, and rash.

Most frequent serious adverse reactions (SAR) in clinical studies in combination with rituximab were pneumonia (17 percent), pyrexia (9 percent), sepsis (8 percent), febrile neutropenia (5 percent), and diarrhea (5 percent); SAR were reported in 49 percent of patients and 10 percent of patients discontinued due to adverse reactions. Most frequent SAR in clinical studies when used alone were pneumonia (15 percent), diarrhea (11 percent) and pyrexia (9 percent); SAR were reported in 50 percent of patients and 53 percent of patients discontinued or interrupted therapy due to adverse reactions.

Most common lab abnormalities (incidence ≥30 percent; all grades) in clinical studies were neutropenia, hypertriglyceridemia, hyperglycemia, and ALT/AST elevations.

Drug Interactions

CYP3A inducers: Avoid coadministration with strong CYP3A inducers.
CYP3A inhibitors: When coadministered with strong CYP3A inhibitors, monitor closely for Zydelig toxicity.
CYP3A substrates: Avoid coadministration with CYP3A substrates.

Dosage and Administration

Adult starting dose: One 150 mg tablet twice daily, swallowed whole with or without food. Continue treatment until disease progression or unacceptable toxicity. The safe dosing regimen for patients who require treatment longer than several months is unknown.

Dose modification: Consult the Zydelig full Prescribing Information for dose modification and monitoring recommendations for the following specific toxicities: pneumonitis, ALT/AST elevations, bilirubin elevations, diarrhea, neutropenia, and thrombocytopenia. For other severe or life-threatening toxicities, withhold Zydelig until toxicity is resolved and reduce the dose to 100 mg, twice daily, upon resuming treatment. If severe or life-threatening toxicities recur upon rechallenge, Zydelig should be permanently discontinued.

– See more at: View Source;p=irol-newsArticle&ID=2120907#sthash.o1KWj2K5.dpuf