On May 28, 2015 Pharmacyclics reported the initiation of PCYC-1136-CA, a multi-center study that will investigate the use of ibrutinib (IMBRUVICA) in combination with MEDI4736, an investigational anti-PD-L1 immune checkpoint inhibitor being developed by AstraZeneca (Press release, Pharmacyclics, MAY 28, 2015, View Source [SID:1234504864]). The Phase Ib/II study will examine the safety, tolerability and effectiveness of this investigational combination in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL). IMBRUVICA is jointly developed and commercialized by Pharmacyclics and Janssen Biotech, Inc.

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"While there has been a great deal of progress in developing therapies to treat certain B-cell malignancies, additional treatment options for the most refractory types of blood cancers are still needed," said Darrin Beaupre, M.D., Ph.D., Head of Early Development and Immunotherapy at Pharmacyclics. "Given the pre-clinical activity we have observed by combining therapies such as ibrutinib and immunotherapy agents, we are excited to investigate the potential to improve the outcomes of patients who are no longer benefitting from the currently available therapies."

The Phase Ib portion of the study will primarily seek to determine the safety, tolerability, and appropriate dose of ibrutinib when combined with MEDI4736 to treat individuals with R/R DLBCL or FL. The Phase II portion of the study will be conducted in two distinct cohorts to determine the safety and effectiveness of the treatment combination in patients with these types of blood cancer.

The clinical study will aim to enroll approximately 109 patients at several sites in the U.S. To learn more about the clinical study, visit: www.clinicaltrials.gov or call Pharmacyclics Medical Information at 877-877-3536.

About IMBRUVICA

IMBRUVICA is currently approved for the treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy, all CLL patients (including treatment-naive) who have del 17p, a genetic mutation that occurs when part of chromosome 17 has been lost, and all patients (including treatment-naive) with Waldenstrom’s macroglobulinemia.1 IMBRUVICA is also approved for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Accelerated approval was granted for the MCL indication based on overall response rate. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials.1

IMBRUVICA (ibrutinib) is a first-in-class, oral, once-daily therapy that inhibits a protein called Bruton’s tyrosine kinase (BTK).1 IMBRUVICA was one of the first medicines to receive U.S. FDA approval via the new Breakthrough Therapy Designation pathway, and is the only product to have received three Breakthrough Therapy Designations.

BTK is a key signaling molecule in the B-cell receptor signaling complex that plays an important role in the survival and spread of malignant B cells.1,2 IMBRUVICA blocks signals that tell malignant B cells to multiply and spread uncontrollably.1

IMBRUVICA is being studied alone and in combination with other treatments in several blood cancers. More than 6,100 patients have been treated in clinical trials of IMBRUVICA conducted in 35 countries by more than 800 investigators. Currently, 13 Phase III trials have been initiated with IMBRUVICA and 67 trials are registered on www.clinicaltrials.gov.

To learn more about the medical terminology used in this news release, please visit View Source

IMPORTANT SAFETY INFORMATION

Warnings and precautions include hemorrhage, infections, cytopenias, atrial fibrillation, second primary malignancies, Tumor Lysis Syndrome and embryo-fetal toxicity.

The most common adverse reactions ( > 25%) in patients with B-cell malignancies (MCL, CLL, WM) were thrombocytopenia, neutropenia, diarrhea, anemia, fatigue, musculoskeletal pain, bruising, nausea, upper respiratory tract infection, and rash. For additional important safety information, please see Important Safety Information to the right and the full Prescribing Information at www.imbruvica.com/downloads/Prescribing_Information.pdf.

On May 28, 2015 Pfizer reported the launch of a competitive, peer-reviewed grants program to support clinical research projects investigating IBRANCE (palbociclib) in advanced breast cancer (Press release, Pfizer, MAY 28, 2015, View Source [SID:1234504863]).

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The multi-year program, which will award a total of up to $3 million in grants to investigators in the United States, is an extension of Pfizer’s Advancing Science through Pfizer Investigator Research Exchange (ASPIRE) initiative. It is the first ASPIRE program to focus on breast cancer research.

IBRANCE received accelerated approval by the U.S. Food and Drug Administration in February 2015 for use in combination with letrozole for the treatment of 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.

"We believe the ASPIRE Breast Cancer Research Awards will contribute important information to our body of knowledge about the role IBRANCE plays in the treatment and clinical management of advanced breast cancer, and will complement the robust clinical development program we have ongoing," said Dr. Julia Perkins Smith, senior medical director, U.S. Breast Cancer Lead, Pfizer Oncology. "Through these awards, we also look forward to supporting the mission of the ASPIRE program to further academic research and nurture the career development of emerging investigators in a disease area of high unmet medical need."

"This is an exciting opportunity to gain a better understanding of the efficacy and tolerability of CDK inhibition in ER+ breast cancer," said Dr. Ruth O’Regan, head of hematology and oncology in the Department of Medicine at the University of Wisconsin School of Medicine and Public Health.

Grantees will be selected through a competitive application process overseen by an independent review panel of breast cancer experts.

The review panel encourages investigators (with a special interest for emerging researchers at Assistant Professor level or equivalent) to submit applications for innovative research in several areas. Highlights of the research of interest include:

Improving the medical knowledge of palbociclib in the treatment of advanced breast cancer
Optimizing clinical management during palbociclib treatment that addresses or improves patient compliance and convenience and/or patient reported outcomes
For more information about the ASPIRE Breast Cancer Research Awards and specifics regarding eligible areas of research, please visit www.aspireresearch.orgExternal Links icon. The application submission period ends September 8, 2015, and successful awardees will be notified in October. Pfizer anticipates providing up to six awards to investigators in the United States.

About IBRANCE

IBRANCE is an oral inhibitor of cyclin-dependent kinases (CDKs) 4 and 6.1 CDKs 4 and 6 are key regulators of the cell cycle that trigger cellular progression.2,3 IBRANCE is indicated in the U.S. for use in combination with letrozole for the treatment of 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. The effectiveness of IBRANCE in these patients is based on a study that measured progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

The full prescribing information for IBRANCE can be found at www.IBRANCE.comExternal Links icon. IBRANCE is not approved for any indication in any market outside the U.S.

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).