Bavencio-Inlyta Combo Recommended for Approval in EU for Advanced Kidney Cancer

The Committee for Medicinal Products for Human Use (CHMP), an arm of the European Medicines Agency, has recommended that a combination of Bavencio (avelumab) and Inlyta (axitinib) be approved for the first-line treatment of adults with advanced renal cell carcinoma, the most common form of kidney cancer.

That recommendation is based on results from the ongoing JAVELIN Renal 101 Phase 3 trial (NCT02684006). The Bavencio-Inlyta combination extended the time people lived without disease worsening — and increased the proportion of patients responding to treatment as compared with the standard of care therapy Sutent (sunitinib).

The European Commission will now review the committee’s recommendation, and is expected to announce a final decision by year’s end.

“Today’s positive CHMP opinion is a significant step toward potentially transforming the treatment landscape and bringing much needed options to people living with advanced renal cell carcinoma in Europe,” Luciano Rossetti, head of global R&D for EMD Serono, said in a press release.

Bavencio, jointly developed by Merck KGaA (operating as EMD Serono in the U.S. and Canada) and Pfizer, is an immune checkpoint inhibitor. It binds to the PD-L1 molecule, which is produced by cancer cells to prevent the immune system from recognizing them. By inhibiting PD-L1, Bavencio exposes the cancer cells, boosting the body’s immune surveillance mechanisms.

Inlyta, by Pfizer, is a tyrosine kinases inhibitor (TKI) that blocks proteins that are implicated in the formation of blood vessels and tumor growth.

JAVELIN Renal 101 enrolled 886 patients with advanced renal cell carcinoma. Participants were randomly assigned to receive Bavencio infusions every two weeks plus oral Inlyta twice daily, or oral Sutent, given once daily, four weeks on/two weeks off.

The trial’s main goal was to determine if the combination was better than Sutent at extending survival outcomes among individuals whose tumors were positive for the PD-L1 factor. Both overall survival and progression-free survival — the time patients live without disease progression — were assessed.

PD-L1 is normally used to predict responses to therapies like Bavencio. Therefore, these patients were expected to respond more strongly to the combination.

Indeed, results published this year in the New England Journal of Medicine showed that Bavencio-treated patients with PD-L1-positive tumors lived without disease worsening a median of 13.8 months, compared with 7.2 months for those receiving Sutent. That represents a 39% reduction in the risk of disease progression or death.

At the time of the analysis, a similar proportion of people with PD-L1-positive tumors were alive in each group — 86.3% for the combination vs. 84.8% for Sutent. But more patients had responded to the combination (55%) than to Sutent (26%).

A broader analysis among all participants continued to demonstrate the combination’s superiority. People receiving the combo therapy lived a median of 13.8 months without disease worsening, compared with 8.4 months for Sutent. Similar benefits were seen across patient risk subgroups.

“We believe that the combination of Bavencio plus [Inlyta] has the potential to help address a significant need for patients with advanced renal cell carcinoma for first-line treatments with a benefit across all prognostic risk groups, and we look forward to a decision from the European Commission,” Rossetti said.

In May, the U.S. Food and Drug Administration (FDA) approved Bavencio plus Inlyta for a similar indication. Merck KGaA and Pfizer also have submitted a request to Japanese regulatory authorities seeking the combination’s approval for unresectable or metastatic renal cell carcinoma.

“Kidney cancer represents a significant burden in Europe, where incidence rates are among the highest in the world,” said Chris Boshoff, MD, PhD, chief development officer of oncology at Pfizer global product development. “Pfizer has been a leader in the development of kidney cancer treatments for more than a decade, and it is a privilege to continue our efforts to bring a new treatment option to this community.”