Old guard meets new as Pfizer and Merck start PDL1-TKI combo trial for kidney cancer

Pfizer VP Chris Boshoff

Pharma giant Pfizer ($PFE) and Germany's Merck are beginning late-stage studies that will see a traditional TKI drug matched up with a new immunotherapy for renal cell carcinoma patients.

Pfizer will bring its marketed kidney cancer drug Inlyta to the table while Darmstadt-based Merck will introduce its experimental anti-PD-L1 drug avelumab to the mix as a first-line treatment for patients with advanced renal cell carcinoma (RCC), a type of kidney cancer.

The two companies announced today that the first patient has been now been treated in the Phase III Javelin Renal 101 study. It is the first and only late-stage trial combining an anti-PD-L1 immunotherapy with a vascular endothelial growth factor (VEGF)-receptor TKI in this setting.

This builds on the breakthrough designation the FDA gave avelumab last year for Merkel cell carcinoma, a rare form of skin cancer with poor outcomes, and comes as Pfizer looks to muscle in on the immuno-oncology space with much help from its European partner.

Chris Boshoff, VP and head of early development, translational and immuno-oncology at Pfizer Oncology, said: "As renal cell carcinoma is an immunogenic type of tumor 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."

The Javelin study is being run as an open-label RCT to see whether it can help patients achieve better progression-free survival rates than Pfizer's blockbuster RCC pill Sutent, also a TKI that targets a host of mutations.

"The first patient receiving treatment in this pivotal trial marks an important milestone in the strategic immuno-oncology alliance between Merck and Pfizer," added Alise Reicin, 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."

Inlyta, which is approved as a second-line treatment for RCC in the U.S. and EU, made Pfizer around $430 million in 2015, a steady 5% rise on the year-before period. It is designed to shore up future loss of sales from the $1.2 billion a year first-line drug Sutent, the standard of care for RCC, when it begins to lose its patents in the future.

TKI, anti-VEGF and other similar drugs, which include big hitters such as Roche's ($RHHBY) multilicensed Avastin and AstraZeneca's ($AZN) lung cancer treatment Iressa, are fast becoming the "old way" of creating drugs, as they can only treat a sub-population of patients with specific genetic mutations.

Avelumab represents the "new way" by focusing on allowing a patient's immune system to recognise and destroy cancerous cells via a checkpoint inhibitor. Anti PD-1 and PD-L1 drugs are predicted to be the next big class in oncology, with total sales expected to hit around $30 billion by the next decade.

Merck & Co ($MRK) and BMS ($BMY) gained first approval for this new class back in 2014 with Roche and AstraZeneca now playing catch-up. Roche was in fact last month granted a speedy FDA review for its PD-L1 bladder cancer treatment atezolizumab. The drug is also being tested in RCC, but is at a much earlier stage.

Pfizer had not been on the original bandwagon for this class but is now playing catch-up with avelumab. The two companies are also testing the drug in ovarian, gastric, lung and bladder cancer settings. Carving out a stake in these markets would go some way toward justifying the $850 million Pfizer handed over to buy into Merck's immunotherapy pipeline back in 2014.

- see the release