Bristol-Myers Squibb, Pharmacyclics, Inc. and Janssen Research & Development, LLC 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 (nivolumab) in combination with Imbruvica (ibrutinib), an oral Bruton’s tyrosine kinase (BTK) inhibitor co-developed and co-marketed by Pharmacyclics and Janssen.

The Phase I/II 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, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL).

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

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 a 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 non-Hodgkin lymphoma. 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, 2014, Ono Pharmaceutical Co. announced that Opdivo received manufacturing and marketing approval in Japan for the treatment of patients with unresectable melanoma. Bristol-Myers Squibb has proposed the name Opdivo, which if approved by health authorities, will serve as the trademark for nivolumab.

In 2011, through a collaboration agreement with Ono Pharmaceutical, Bristol-Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally except in Japan, South Korea, and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Bristol-Myers Squibb and Ono Pharmaceutical further expanded the companies' strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies, as single agents and combination regimens, for patients with cancer in Japan, South Korea, and Taiwan.

On September 26, 2014, Bristol-Myers Squibb announced that the FDA accepted for priority review the biologics license application for for Opdivo 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 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.

Imbruvica, jointly developed and commercialized by Janssen Biotech, Inc. and Pharmacyclics, 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. It is also approved for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Imbruvica is being studied alone and in combination with other treatments in several blood cancers including CLL, MCL, Waldenström’s macroglobulinemia (WM), DLBCL, FL and multiple myeloma (MM).

Source: Bristol-Myers Squibb