Pfizer, Merck Combination Therapy Shows Significant Improvement in Phase III

Clear Cell Carcinoma

Microscopic image of clear cell carcinoma, the most common type of renal cell carcinoma. It is characterized by cytoplasmic clearing and a pattern of small branching blood vessels.

Late-stage trial results show that a combination of Bavencio (avelumab) and Inlyta (axitinib) significantly improved progression-free survival in previously untreated patients with advanced renal cell carcinoma.

The Phase III JAVELIN Renal 101 study is being conducted by Merck KGaA and Pfizer. The progression-free survival news was announced following an interim analysis by an independent Data Monitoring Committee. The data showed the statistically significant response in patients whose tumors had programmed death ligand-1‒positive (PD-L1+) expression greater than 1 percent, as well as study patients regardless of PD-L1 tumor expression.

Bavencio is a human anti-programmed death ligand-1 (PD-L1) antibody. In preclinical models, Bavencio has been shown to release the suppression of the T cell-mediated antitumor immune. The drug has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro, according to data provided by the companies. Pfizer’s Inlyta has been approved in the United States as a second-line monotherapy for the treatment of advanced RCC.

This morning the two companies said if PFS was statistically significant in the PD-L1+ subgroup, then “PFS in the entire study population was to be analyzed for statistical significance.” The study is expected to continue as planned until the final analysis can reveal the other primary endpoint of overall survival, the companies said this morning. Following the interim results, Merck KGaA and Pfizer said they intend to pursue a regulatory submission in the United States based on the results they have seen so far. The companies added that a detailed analysis of the interim results will be submitted for presentation at an upcoming medical conference.

Chris Boshoff, head of immuno-oncology, early development and translational oncology at Pfizer, said the JAVELIN Renal 101 trial is the “first positive Phase III study” that combines an immune checkpoint blocker with a tyrosine kinase Inhibitor. That data supports the potential combination of Bavencio and Inlyta as a “new cancer treatment approach for patients with advanced RCC,” Boshoff said.

“These positive results reinforce Pfizer’s long-standing heritage in advancing standards of care for people with RCC, and we look forward to discussing these data in greater detail with health authorities,” Boshoff said in a statement.

RCC is the most common form of kidney cancer, with the most common form of RCC being clear cell carcinoma. That type of RCC accounts for about 70 percent of all renal cell carcinoma cases, the two companies said. Between 20 and 30 percent of patients are diagnosed at the metastatic stage, which means first-year survival rates for those patients is about 12 percent, the companies said. Both Merck KGaA and Pfizer said the outlook for these patients is poor.

The combination treatment received the U.S. Food and Drug Administration’s Breakthrough Therapy Designation in December 2017.

Luciano Rosetti, global head of research and development at Merck KGaA, said the data released today illustrates the impact the combination therapy can have as a potential first-line treatment for people with advanced renal cell carcinoma.

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