The U.S. Food and Drug Administration (FDA) has approved Bavencio (avelumab) to treat patients with locally advanced or metastatic urothelial carcinoma whose disease progressed during or following platinum-based chemotherapy, or who had disease progression within 12 months of platinum-based chemo, administered before or after surgery.
This is the second worldwide approval of Bavencio, a PD-L1 inhibitor jointly developed by Merck and Pfizer. The first, granted in March 2017, was an accelerated approval for patients with Merkel cell carcinoma, a rare and aggressive type of skin cancer. Continued approval for this indication is contingent upon confirmation of clinical benefits in clinical trials.
“This approval for Bavencio in patients with locally advanced or metastatic urothelial carcinoma exemplifies our unwavering commitment to finding new treatments for the most challenging cancers,” Dr. Luciano Rossetti, executive vice-president, at Merck’s R&D unit in Darmstadt, Germany, said in a news release. “Coming just a few weeks after the approval for metastatic Merkel cell carcinoma, we continue to demonstrate our ability to accelerate access to innovative medicines for patients in need.”
Advanced urothelial carcinoma is an aggressive disease with a high rate of recurrence. Only 5 percent of patients live for more than five years after the cancer spreads to other regions of the body — and at present, no drugs were available to help them.
“Once urothelial carcinoma progresses after treatment with chemotherapy, the five-year survival rate is alarmingly low,” said Dr. Andrea Apolo of the National Cancer Institute in Bethesda, Maryland. “Until recently, there had been limited innovation in urothelial carcinoma, and this approval gives us another treatment to help battle this aggressive disease.”
The FDA based its approval on data from the JAVELIN trial (NCT01772004), a Phase 1, open-label, single-arm, dose-ascending study, designed to evaluate the safety and efficacy of Bavencio in multiple solid tumors.
The urothelial carcinoma cohorts included 242 patients with locally advanced or metastatic disease who had progressed during or following platinum-based chemotherapy, or who had disease progression within one year of adjuvant or neoadjuvant platinum-based chemotherapy.
Patients were included regardless of their PD-L1 status, and received Bavencio (10 mg/kg) intravenously every two weeks until disease progression or unacceptable toxicity. The study’s primary endpoint was to establish a dose limiting toxicity and to determine the best overall response. Secondary outcomes included confirmed overall response rate, duration of response, overall survival, progression-free survival and safety.
Among the 226 patients evaluated for efficacy, 44 percent had non-bladder urothelial cancer and 83 percent had visceral metastasis, including 34 percent with liver metastasis. Although Bavencio demonstrated its safety and efficacy in this patient population, neither Merck nor Pfizer disclosed any trial results. Instead, data will be presented at an upcoming medical meeting.
“This approval builds on the ongoing clinical development program for Bavencio in urothelial carcinoma and reinforces our commitment to providing new medicines to patients with difficult-to-treat cancers,” said Liz Barrett, global president at Pfizer Oncology. “By drawing on the strength of the alliance, as well as Pfizer’s deep experience in genitourinary cancers, we believe Bavencio will be an important treatment option, and we hope it will help to improve outcomes for these patients.”
Currently, a Phase 3 is evaluating Bavencio plus best supportive care versus best supportive care alone in patients with locally advanced or metastatic urothelial cancer who did not have disease progression following first-line platinum-based chemotherapy. The multicenter, global, randomized JAVELIN Bladder 100 study (NCT02603432) is now enrolling participants.