Pfizer Inc. has agreed with Merck & Co., Inc., known as MSD outside the United States and Canada, through two Merck subsidiaries, to explore the therapeutic potential of Merck’s investigational anti-PD-1 therapy, MK-3475, in combination with two Pfizer oncology assets. A phase I/II clinical study will evaluate the safety and anti-cancer efficacy of MK-3475 combined with Pfizer’s axitinib (INLYTA) in renal cell carcinoma (RCC).

A separate phase I study will evaluate the safety and tolerability of the combination of MK-3475 and PF-05082566 (PF-2566), Pfizer’s investigational, fully humanized monoclonal antibody (mAb) that stimulates signalling through 4-1BB (CD-137), a protein involved in regulation of immune cell proliferation and survival.

“There has been notable progress in the cancer immunotherapy field over the last year, with new clinical data showing promising efficacy and tolerability for emerging therapies – particularly those that target the PD-1 pathway,” said Dr Mace Rothenberg, senior vice president of Clinical Development and Medical Affairs and chief medical officer for Pfizer Oncology. “These investigational therapies, which harness the body’s immune system to treat disease, may hold the greatest potential for patients with cancer when used in combination with other immuno-oncology agents, like PF-2566, to amplify anti-tumor immune responses, or with targeted agents, like axitinib, to optimize their effectiveness.  We are pleased to collaborate with Merck to study a diverse group of our anti-cancer agents in combination with MK-3475, with the goal of identifying more efficacious treatment options for patients.”

“We are pleased to be collaborating with Pfizer to study MK-3475 as part of these novel combination regimens,” said Dr Eric Rubin, vice president, clinical development for oncology, Merck Research Laboratories. “Early evaluation of immunotherapeutic combinations is important toward potentially accelerating the development of new options for patients with cancer.”

Pfizer will conduct the clinical studies of MK-3475 plus axitinib and MK-3475 plus PF-2566.  This agreement does not provide for any collaboration between Pfizer and Merck following the completion of the specified studies.

Financial terms were not disclosed.  

Under a separate agreement Pfizer and Merck are currently exploring the pre-clinical combination of MK-3475 with Pfizer’s investigational therapy palbociclib (PD-0332991).  Merck is conducting these pre-clinical studies.  Further studies would depend on the outcome of the ongoing pre-clinical studies as well as subsequent agreement by Merck and Pfizer.

Many tumours are able to evade the immune system through a mechanism that exploits the PD-1 inhibitory checkpoint protein. MK-3475 is an investigational, highly selective anti-PD-1 immunotherapy designed to restore the natural ability of the immune system to recognize and target cancer cells by selectively achieving dual ligand blockade (PD-L1 and PD-L2) of the PD-1 protein. By blocking PD-1, MK-3475 enables activation of the immune system’s T-cells that target cancer by essentially releasing a brake on the immune system.

INLYTA, a kinase inhibitor, is an oral therapy that is designed to inhibit tyrosine kinases, including vascular endothelial growth factor (VEGF) receptors 1, 2 and 3; these receptors can influence tumour growth, vascular angiogenesis and progression of cancer (the spread of tumours). In the United States, INLYTA is approved for the treatment of advanced renal cell carcinoma (RCC) after failure of one prior systemic therapy. INLYTA is also approved by the European Medicines Agency (EMA) for use in the European Union (EU) in adult patients with advanced RCC after failure of prior treatment with sunitinib or a cytokine.

PF-2566 is an investigational, fully human monoclonal antibody (mAb) that targets CD-137, a protein expressed in many immune cells. In pre-clinical models, it has shown anti-tumour activity by enhancing T-cell mediated immune responses. Pfizer is currently evaluating PF-2566 in a phase I study as a single agent in multiple tumour types, as well as in combination with rituxumab in non-Hodgkin lymphoma patients. PF-2566 is not approved for any indications in any markets.

Palbociclib is an investigational, oral and selective inhibitor of cyclin dependent kinases 4 and 6. In April 2013, palbociclib received Breakthrough Therapy designation by the FDA for the potential treatment of patients with advanced breast cancer. Palbociclib is not approved for any indications in any markets.

Pfizer Oncology is committed to the discovery, investigation and development of innovative treatment options to improve the outlook for cancer patients worldwide.