Phase 3 Interim Analysis Shows Improved Survival in Patients with Bladder Cancer

Patients with previously untreated locally advanced or metastatic urothelial carcinoma treated with Bavencio (avelumab) and best supportive care as a first-line maintenance therapy experienced significantly longer survival, compared with best supportive care alone, according to an interim analysis of the phase 3 JAVELIN Bladder 100 study.

Moreover, improved overall survival was seen among the co-primary populations: all randomized patients and patients with PD-L1—positive tumors.

"Our unique maintenance approach with Bavencio has significantly prolonged survival for patients with locally advanced or metastatic urothelial carcinoma in this trial," Dr. Luciano Rossetti, executive vice president and head of Global R&D for the Biopharma business of Merck, said in a press release. "We believe this approach could become part of routine clinical practice, as these results are a major advance on the existing standard of care."

With this, the trial met its primary endpoint of overall survival at the planned interim analysis of patients whose disease did not progress on induction chemotherapy. In addition, the safety profile of Bavencio appeared consistent to those seen in the JAVELIN monotherapy clinical development program.

The multicenter, multinational, randomized, open-label, parallel-arm phase 3 trial is designed to evaluate Bavencio as a frontline maintenance therapy following best standard care, compared with best standard care alone in 700 patients with locally advanced or metastatic UC whose disease did not progress after completion of first-line platinum-containing chemotherapy.

The primary endpoint is overall survival in co-primary populations of all patients and patients with PD-L1-positive tumors. Secondary endpoints include progression-free survival (the time from treatment to disease progression or worsening), anti-tumor activity, safety, pharmacokinetics, immunogenicity, predictive biomarkers and patient-reported outcomes in the co-primary populations.

"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," Dr. Chris Boshoff, chief development officer of oncology at Pfizer Global Product Development, said in the release.

Merck and Pfizer plan to present these results at an upcoming medical meeting. “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,” Boshoff added.

Urothelial carcinoma, which accounts for 90% of bladder cancers, has a high initial response to standard-of-care therapy; however, durable and complete responses following first-line chemotherapy are uncommon. These patients tend to experience disease progression within nine months of treatment, for which the five-year survival rate if 5%.