A combination of Bavencio (avelumab) and Inlyta (axitinib) significantly extends the time to disease progression or death in patients with untreated, advanced renal cell carcinoma (RCC), according to top-line results of a Phase 3 trial announced by Merck and Pfizer.
The trial compared the combination with the standard of care Sutent (sunitinib). Benefits were seen both in patients with PD-L1-positive tumors — which may indicate they will respond to immune checkpoint inhibitors — and the overall study participants regardless of PD-L1 status.
The JAVELIN Renal 101 Phase 3 study (NCT02684006) is a global multicenter, randomized trial assessing the anti-tumor activity and safety of Bavencio — jointly developed by Pfizer and Merck KGaA, which is EMD Serono in the U.S. and Canada — in combination with Pfizer’s Inlyta, compared with standalone Sutent (also by Pfizer) in 886 patients with advanced RCC.
Patients took 10 mg/kg Bavencio through intravenous infusion every two weeks, combined with 5 mg/kg of oral Inlyta twice per day, or 50 mg of oral Sutent once daily, four weeks on/two weeks off.
Bavencio is part of a group of therapies called immune checkpoint inhibitors. 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.
In turn, Inlyta is a tyrosine kinases inhibitor (TKI), blocking proteins that are implicated in the formation of blood vessels and tumor growth.
“JAVELIN Renal 101 is the first positive Phase 3 study combining an immune checkpoint blocker with a TKI, supporting the potential of Bavencio and Inlyta as a new cancer treatment approach for patients with advanced RCC,” Chris Boshoff, MD, PhD, said in a press release. Boshoff is senior vice president and head of immuno-oncology, early development and translational oncology, Pfizer global product development.
Boshoff also said that the positive findings reinforce the company’s commitment to advance treatments for RCC patients. “We look forward to discussing these data in greater detail with health authorities,” he added.
The trial did not find new safety signals. Adverse events for all three medications were consistent to their known safety profiles. Changes in overall survival — the trial’s other primary goal — will be assessed in the final analysis.
The two companies are planning a regulatory submission to the U.S. Food and Drug Administration (FDA) based on these interim results. They also plan to present a detailed analysis at an upcoming medical conference.
In December 2017, the FDA granted breakthrough therapy designation to the Bavencio and Inlyta combination for untreated advanced RCC patients.
“We are encouraged by these data which illustrate the impact of Bavencio in combination with Inlyta as a potential first-line treatment for people with advanced RCC,” said Luciano Rossetti, MD, Merck KGaA’s executive vice president, global head of research & development at the biopharma business.
“They also support our firm belief in the promise of combining Bavencio with currently approved therapies and novel agents, a strong focus of the overall JAVELIN clinical development program,” Rossetti added.
Bavencio has been granted accelerated approval by the FDA for metastatic Merkel cell carcinoma (mMCC), an aggressive skin cancer, and urothelial carcinoma, a type of cancer of the bladder or urinary tract. In Europe, it has been approved as standalone therapy for adults with mMCC.
Inlyta has been approved in the U.S. as a standalone therapy for advanced RCC after failure of one prior systemic treatment, and in Europe for adults with advanced RCC after failure of prior treatment with Sutent or a cytokine, a type of protein essential in immunity.