ROCKLAND, Mass. & NEW YORK—Looking to launch a spear into the heart of urothelial carcinoma (UC), the companies behind the Phase 3 JAVELIN Bladder 100 clinical study report that their study met its primary endpoint of overall survival (OS) at the planned interim analysis.
As noted by the partners—EMD Serono, the biopharmaceutical business of Merck KGaA of Darmstadt, Germany, in the United States and Canada, and Pfizer Inc.—the trial involves patients with previously untreated locally advanced or metastatic UC whose disease did not progress on induction chemotherapy and who were randomized to receive first-line maintenance therapy with Bavencio (avelumab) and best supportive care (BSC) lived significantly longer than those who received BSC only. A statistically significant improvement in OS was demonstrated in the Bavencio arm in each of the co-primary populations: all randomized patients and patients with PD-L1–positive tumors.
The safety profile for Bavencio in the trial was consistent with that in the JAVELIN monotherapy clinical development program. The results of the study will be submitted for presentation at an upcoming medical congress and shared with the U.S. Food and Drug Administration (FDA) and other health authorities.
Importantly, though, is that Bavencio potentially represents a new paradigm in treating UC.
“ Bavencio is the first immunotherapy to demonstrate in a clinical trial a statistically significant improvement in overall survival as a first-line treatment for patients with advanced urothelial carcinoma,” said Dr. Chris Boshoff, chief development officer in the Oncology division of Pfizer Global Product Development. “These latest positive data from the JAVELIN clinical development program add to the body of evidence for Bavencio in the treatment of genitourinary cancers, and we look forward to discussing these results with health authorities.”
Of course, while the compound could set a new standard by becoming a first-line therapy, it isn’t the first immunotherapeutic option for UC. As noted by Dr. Petros Grivas early last year in a Q&A about emerging immunotherapy approaches for urothelial cancer at Cancer Network (online home of the journal Oncology): “I would start by saying that we have experienced a revolution in the treatment landscape for advanced urothelial cancer in the last few years and this has led to the FDA approval of five distinct immune checkpoint inhibitors that inhibit the PD1/PDL1 axis of the immune system. These five agents are pembrolizumab, atezolizumab, durvalumab, avelumab and nivolumab.”
UC accounts for an overwhelming 90 percent of all bladder cancer; furthermore, when bladder cancer is metastatic, the five-year survival rate is 5 percent. Combination chemotherapy is currently the first-line standard of care for patients with advanced disease, but despite high initial response rates, durable and complete responses following first-line chemotherapy are uncommon, and most patients will ultimately experience disease progression within nine months after initiation of treatment.
“Our unique maintenance approach with Bavencio has significantly prolonged survival for patients with locally advanced or metastatic urothelial carcinoma in this trial,” said Luciano Rossetti, head of Global R&D for EMD Serono. “We believe this approach could become part of routine clinical practice, as these results are a major advance on the existing standard of care.”
In 2017, the FDA approved Bavencio for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy, or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response and duration of response. JAVELIN Bladder 100 is the confirmatory study for the conversion to full approval.