Phase III JAVELIN Bladder 100 Meets Primary Endpoint of Overall Survival

The phase III JAVELIN Bladder 100 study met its primary endpoint of overall survival (OS) at the planned interim analysis for the first-line maintenance treatment of patients with previously untreated locally advanced or metastatic urothelial carcinoma whose disease did not progress after completion of first-line platinum-containing chemotherapy, according to EMD Serono (Pfizer), the drug’s manufacturer.

In this parallel-arm study, patients were randomly assigned to receive either avelumab (Bavencio) plus best supportive care (BSC) or BSC alone.

“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,” Chris Boshoff, MD, PhD, chief development officer of Oncology at Pfizer Global Product Development, said in a press release. “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.” 

A statistically significant improvement in OS was observed in the avelumab arm in each of the co-primary populations: all randomized patients and patients with PD-L1-positive tumors. Additionally, the safety profile for avelumab in the trial was consistent with that demonstrated in the JAVELIN monotherapy clinical development program.

Results from this study will be submitted for presentation at an upcoming medical congress and shared with the FDA and other health authorities. 

“Our unique maintenance approach with Bavencio has significantly prolonged survival for patients with locally advance or metastatic urothelial carcinoma in this trial,” Luciano Rossetti, head of Global R&D for EMD Serono, said in the 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.” 

The most common adverse cents (AEs; all grades, ≥20%) were fatigue (41%), infusion-related reaction (30%), musculoskeletal pain (25%) nausea (25%) decreased appetite/hypophagia (21%), and urinary tract infection (21%).

Selected laboratory abnormalities (grades 3-4, ≥3%) were hyponatremia (16%), increased gamma-glutamyltransferase (12%), lymphopenia (11%), hyperglycemia (9%), increased alkaline phosphatase (7%), anemia (6%), increased lipase (6%), hyperkalemia (3%), and increased aspartate aminotransferase (3%). 

In 2017, the FDA approved avelumab 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 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; this study is the confirmatory study for the conversion to approval. 

Reference:

BAVENCIO Significantly Improved Overall Survival in Patients With Locally Advanced or Metastatic Urothelial Carcinoma [news release]. Rockland, Massachusetts and New York. Published January 6, 2020. prnewswire.com/news-releases/bavencio-significantly-improved-overall-survival-in-patients-with-locally-advanced-or-metastatic-urothelial-carcinoma-300981078.html. Accessed January 6, 2020.