Merck and Pfizer announced the treatment of the first patient in a phase III study of avelumab, an investigational fully human anti-PD-L1 IgG1 monoclonal antibody, in an advanced renal cell carcinoma (RCC) setting.

The study, JAVELIN Renal 101, is the first pivotal trial investigating avelumab in combination with Inlyta (axitinib), a tyrosine kinase inhibitor (TKI), in patients with previously untreated advanced RCC, and the only phase III trial currently evaluating an anti-PD-L1 immunotherapy in combination with a vascular endothelial growth factor (VEGF)-receptor TKI in this setting. The 5-year survival rate for patients with distant metastatic RCC is approximately 12 per cent.

“Pfizer has a strong heritage in the treatment of metastatic RCC, and through the strategic alliance with Merck, we aim to further accelerate the development of potential therapies to help improve the lives of patients living with this disease,” said Chris Boshoff, M.D., PhD., vice president and head of early development, translational and immuno-oncology at Pfizer Oncology. “As renal cell carcinoma is an immunogenic type of tumour that can respond to immunotherapy and to anti-angiogenic treatment, there is a strong scientific rationale for combining avelumab with Inlyta and we believe that this combination may help improve outcomes for patients with this cancer.”

JAVELIN Renal 101 is a multicenter, international, randomized (1:1), open-label phase III trial designed to evaluate the potential superiority, assessed by the progression-free survival (PFS), of first-line avelumab combined with Inlyta compared with Sutent (sunitinib malate) monotherapy, an oral, small-molecule, multi-targeted receptor TKI, in patients with unresectable, locally advanced or metastatic RCC with clear cell component. The study will enroll 583 patients across approximately 170 sites in Asia, Europe, Latin America and North America.

“The first patient receiving treatment in this pivotal trial marks an important milestone in the strategic immuno-oncology alliance between Merck and Pfizer,” said Alise Reicin, M.D., head of global clinical development at the biopharma business of Merck. “As part of the JAVELIN clinical development program, we are exploring the potential of innovative, rational combination therapies, which combine avelumab with other treatment modalities to address significant unmet needs that exist in challenging cancers, such as advanced renal cell carcinoma.”

The clinical development programme for avelumab now includes more than 1,600 patients who have been treated across more than 15 tumor types.

Inlyta is currently approved in the United States for the treatment of advanced RCC after failure of one prior systemic therapy. Inlyta is also approved by the European Medicines Agency for use in the European Union in adult patients with advanced RCC after failure of prior treatment with Sutent or a cytokine. Following its approval in 2012, Inlyta has become a standard of care for second-line advanced RCC and has been used by an estimated 12,000 metastatic renal cell carcinoma patients in the United States. Inlyta is under investigation in combination with avelumab for the indication studied in this phase III trial.

Renal cell carcinoma accounts globally for 2-3% of all malignancies. As of 2012, more than 338,000 new cases of kidney cancer were diagnosed per year worldwide. In general, higher incidence rates of renal cell carcinoma occur in Eastern Asia, North America and Central/Eastern Europe. Early-stage renal cancers tend to have a better prognosis, compared with advanced/metastatic renal cancers.

Avelumab (also known as MSB0010718C) is an investigational fully human anti-PD-L1 IgG1 monoclonal antibody. By inhibiting PD-L1 interactions, avelumab is thought to enable the activation of T-cells and the adaptive immune system. By retaining a native Fc-region, avelumab is thought to potentially engage the innate immune system and induce antibody-dependent cell-mediated cytotoxicity (ADCC). In November 2014, Merck and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.

Inlyta is indicated for the treatment of advanced RCC after failure of one prior systemic therapy. 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).

Sutent is an oral multi-kinase inhibitor that works by blocking multiple molecular targets implicated in the growth, proliferation and spread of cancer. Sutent was approved in 2006 and is indicated for the treatment of advanced/metastatic renal cell carcinoma.

Immuno-oncology is a top priority for Merck and Pfizer. The global strategic alliance between Merck and Pfizer enables the companies to benefit from each other’s strengths and capabilities and further explore the therapeutic potential of avelumab, an investigational anti-PD-L1 antibody initially discovered and developed by Merck. The immuno-oncology alliance will jointly develop and commercialize avelumab and advance Pfizer’s PD-1 antibody. The alliance is focused on developing high-priority international clinical programmes to investigate avelumab, as a monotherapy, as well as combination regimens, and is striving to find new ways to treat cancer.