On October 13, 2014 Bristol-Myers Squibb Company (NYSE:BMY), Pharmacyclics, Inc. (NASDAQ:PCYC), and Janssen Research & Development, LLC reported that they have entered into a clinical trial collaboration agreement to evaluate the safety, tolerability and preliminary efficacy of Bristol-Myers Squibb’s investigational PD-1 immune checkpoint inhibitor OPDIVO(R) (nivolumab) in combination with IMBRUVICA(R) (ibrutinib), an oral Bruton’s tyrosine kinase (BTK) inhibitor co-developed and co-marketed by Pharmacyclics and Janssen (Press release, Bristol-Myers Squibb, OCT 13, 2014, View Source [SID:SID1234515156]). The Phase 1/2 study will focus on evaluating the safety and anti-tumor activity of combining OPDIVO and IMBRUVICA as a potential treatment option for patients with non-Hodgkin lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). Bristol-Myers Squibb has proposed the name OPDIVO (pronounced op-dee-voh), which if approved by health authorities, will serve as the trademark for the investigational drug, nivolumab.

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OPDIVO is part of a new class of cancer treatments known as immunotherapies, which are designed to harness the body’s own immune system in fighting cancer by targeting distinct regulatory components of the immune system. Each agent has individually shown activity against hematologic malignancies in clinical trials; pre-clinical evidence suggests OPDIVO and IMBRUVICA may have the potential for additive treatment effects in patients with hematologic malignancies.

"Our collaboration to study OPDIVO in combination with IMBRUVICA is an innovative approach to accelerating Bristol-Myers Squibb’s progress in the study of immuno-oncology and hematologic malignancies, gaining further insight into promising areas of drug development and research," stated Michael Giordano, senior vice president, Head of Development, Oncology, Bristol-Myers Squibb. "We look forward to working with Pharmacyclics and Janssen to evaluate the potential of these two therapies as options for patients with lymphomas."

"We are excited about the opportunity to understand and evaluate the potential activity of IMBRUVICA and OPDIVO together, and the benefits this combination may offer patients," said Peter F. Lebowitz, M.D., Ph.D., Global Oncology Head, Janssen. "We look forward to working with Bristol-Myers Squibb and Pharmacyclics on this study as we continue to grow the body of knowledge about IMBRUVICA in different settings and patient populations."

"This collaboration underscores our interest in exploring the use of IMBRUVICA in combination with other therapies to address a variety of histologies in which we believe IMBRUVICA can make a meaningful clinical difference," said Bob Duggan, Chairman and CEO, Pharmacyclics. "We value our strategic collaboration with Janssen and look forward to extending our relationship to Bristol-Myers Squibb for this project as our companies collectively seek to advance treatment options for patients."

The study will be conducted by Janssen. Additional details of the collaboration were not disclosed.

About OPDIVO (nivolumab)

Cancer cells may exploit "regulatory" pathways, such as checkpoint pathways, to hide from the immune system and shield the tumor from immune attack. OPDIVO is an investigational, fully-human PD-1 (programmed death-1) immune checkpoint inhibitor that binds to the checkpoint receptor PD-1 expressed on activated T-cells.

Bristol-Myers Squibb has a broad, global development program to study OPDIVO in multiple tumor types consisting of more than 35 trials – as monotherapy or in combination with other therapies – in which more than 7,000 patients have been enrolled worldwide. Among these are several potentially registrational trials in non-small cell lung cancer (NSCLC), melanoma, renal cell carcinoma (RCC), head and neck cancer, glioblastoma and NHL.

In 2013, the FDA granted Fast Track designation for OPDIVO in NSCLC, melanoma and RCC. In April 2014, the company initiated a rolling submission with the FDA for OPDIVO in third-line pre-treated squamous cell NSCLC and expects to complete the submission by year-end. The FDA granted its first Breakthrough Therapy Designation for OPDIVO in May 2014 for the treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant and brentuximab. On July 4, Ono Pharmaceutical Co. announced that OPDIVO received manufacturing and marketing approval in Japan for the treatment of patients with unresectable melanoma, making OPDIVO the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. On September 26, Bristol-Myers Squibb announced that the FDA accepted for priority review the Biologics License Application for previously treated advanced melanoma, and the Prescription Drug User Fee Act goal date for a decision is March 30, 2015. The FDA also granted OPDIVO Breakthrough Therapy status for this indication. In the European Union, the European Medicines Agency (EMA) has validated for review the Marketing Authorization Application (MAA) for OPDIVO in advanced melanoma. The application has also been granted accelerated assessment by the EMA’s Committee for Medicinal Products for Human Use. The EMA also validated for review the MAA for nivolumab in NSCLC.

About IMBRUVICA(R)

IMBRUVICA(R) (ibrutinib) is a first-in-class, oral, once-daily therapy that inhibits a protein called Bruton’s tyrosine kinase (BTK). 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. IMBRUVICA blocks signals that tell malignant B cells to multiply and spread uncontrollably.

IMBRUVICA is approved for the treatment of patients with CLL who have received at least one prior therapy, and for the treatment of CLL patients with del 17p, a genetic mutation that occurs when part of chromosome 17 has been lost.

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 (ORR). Improvements in survival or disease-related symptoms have not been established. Continued approval for the MCL indication may be contingent upon verification of clinical benefit in confirmatory trials.

IMBRUVICA is being studied alone and in combination with other treatments in several blood cancers including CLL, MCL, Waldenstrom’s macroglobulinemia (WM), DLBCL, FL and multiple myeloma (MM). Approximately 3,500 patients have received IMBRUVICA in clinical trials conducted in 35 countries by more than 800 investigators around the world. As of June 30, 2014, 12 Phase 3 trials have been initiated with IMBRUVICA and approximately 50 trials are registered on www.clinicaltrials.gov. The overall clinical development program in CLL currently includes seven Phase 3 trials and covers all lines of therapy and various combinations of treatments.

IMBRUVICA was one 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. IMBRUVICA is jointly developed and commercialized by Janssen Biotech, Inc. and Pharmacyclics.

IMBRUVICA INDICATIONS

IMBRUVICA is indicated to treat people with:

— Mantle cell lymphoma (MCL) who have received at least one prior therapy
o Accelerated approval was granted for this indication based on overall
response rate. Improvements in survival or disease-related symptoms
have not been established. Continued approval for this indication may
be contingent upon verification of clinical benefit in confirmatory
trials.
— Chronic lymphocytic leukemia (CLL) who have received at least one prior
therapy
— Chronic lymphocytic leukemia (CLL) with 17p deletion

IMBRUVICA – IMPORTANT SAFETY INFORMATION

Warnings and Precautions include hemorrhage, infection, cyptopenias, atrial fibrillation, second primary malignancies, and embryo-fetal toxicity.

The most common adverse reactions include thrombocytopenia, diarrhea, neutropenia, anemia, fatigue, musculoskeletal pain, peripheral edema, upper respiratory tract infection, nausea, bruising, dyspnea, constipation, rash, abdominal pain, pyrexia, vomiting, and decreased appetite.