Ono Pharmaceutical Co.,Ltd., Bristol-Myers Squibb Company and Kyowa Hakko Kirin Co., Ltd. have entered into a clinical trial collaboration agreement to conduct a phase 1 combination study with Opdivo (nivolumab), a PD-1 immune checkpoint inhibitor, and mogamulizumab, an anti-CCR4 antibody.

The study, which will be conducted in Japan, will focus on evaluating the safety, tolerability and anti-tumor activity of combining Opdivo and mogamulizumab as a potential treatment option for patients with advanced or metastatic solid tumors.

“The planned combination study will help determine whether the combination of these two immunotherapies can deliver better outcomes in patients with advanced cancers.”

Opdivo, launched in Japan in September 2014 for the treatment of patients with unresectable melanoma, is being developed in multiple tumor types in more than 50 clinical trials worldwide. Mogamulizumab was launched in Japan in May 2012 for the treatment of relapsed or refractory CCR4-positive Adult T-cell Leukemia-Lymphoma (ATL), and granted the indication expansion in March 2014 for relapsed or refractory CCR4-positive Peripheral T-Cell Lymphoma (PTCL) and Cutaneous T-Cell Lymphoma (CTCL). Clinical trials with mogamulizumab in ATL, PTCL, and CTCL are ongoing in the US, European Union (EU) and other countries.

Opdivo and mogamulizumab are 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. Opdivo binds to the checkpoint receptor PD-1 expressed on activated T-cells, blocking this pathway and enabling the immune system to attack tumors, while mogamulizumab can suppress some of the immune cells that shield the tumor from the immune system. Pre-clinical evidence for each therapy suggests the combination of Opdivo and mogamulizumab may lead to an enhanced anti-tumor immune response compared to either agent alone.

“Studying combination regimens of immunotherapies offers the opportunity to explore the potential of enhanced efficacy compared to current standards of care in treating cancer,” said Hiroshi Awata, Member of the Board of directors, vice president executive officer/executive director, clinical development & clinical development planning, Ono. “We are delighted to be able to pursue the possibility of immunotherapies through this collaboration with Kyowa Hakko Kirin. We believe that there is a strong rationale to explore the combination of Opdivo and mogamulizumab with the goal of identifying a new treatment option for these cancer patients.”

“Our collaboration with Kyowa Hakko Kirin further complements the broad clinical development program for Opdivo, will advance our understanding of the combination of Opdivo and mogamulizumab, and is an example of our commitment to develop combination immuno-oncology regimens for patients with metastatic cancer,” stated Michael Giordano, senior vice president, Head of Development, Oncology, Bristol-Myers Squibb.

“It is exciting for us to build a partnership with Ono and Bristol-Myers Squibb in immuno-oncology,” said Yoichi Sato, managing executive officer, vice president, head of research and development division of Kyowa Hakko Kirin. “The planned combination study will help determine whether the combination of these two immunotherapies can deliver better outcomes in patients with advanced cancers.”

The study will be conducted by Ono and Kyowa Hakko Kirin. Additional details of the collaboration were not disclosed.

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, human PD-1 immune checkpoint inhibitor that binds to the checkpoint receptor PD-1 expressed on activated T-cells.

Opdivo is being studied across multiple tumor types in more than 50 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 non-Hodgkin lymphoma (NHL).

In 2012, 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 Opdivo Breakthrough Therapy Designation 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 and launched on September 2, making Opdivo the first PD-1 immune checkpoint inhibitor approved and launched 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 EU, 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 Opdivo in NSCLC.

Mogamulizumab ( Poteligeo) is a novel, humanized mAb directed against CC chemokine receptor type 4 (CCR4). Engineered by Kyowa Hakko Kirin's unique Potelligent Technology, the antibody is designed to kill its target cells through potent antibody-dependent cellular cytotoxicity. Mogamulizumab was launched in Japan in May 2012 for the treatment of patients with relapsed or refractory CCR4-positive adult T-cell leukemia-lymphoma (ATL). The drug was approved for indication expansion and was granted marketing authorization in Japan for the treatment of patients with relapsed or refractory CCR4-positive, peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL) in March 2014. Clinical trials with mogamulizumab in ATL, PTCL, and CTCL are ongoing in the US, EU and other countries.

Ono Pharmaceutical headquartered in Osaka, Japan, is an R&D-oriented pharmaceutical company committed to creating innovative medicines in specific areas.

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases.

Kyowa Hakko Kirin is a leading biopharmaceutical company in Japan focusing on its core business area of oncology, nephrology and immunology/allergy.