Avelumab Granted Priority Review by the FDA for Metastatic Urothelial Carcinoma

Avelumab was granted a priority review to a biologics license application (BLA) by the Food and Drug Administration (FDA) for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) whose disease progressed after platinum-based therapy, according to Merck KGaA and Pfizer, the codevelopers of the PD-L1 inhibitor.

The priority review is based on data from the JAVELIN international development program of avelumab. In the JAVELIN solid tumor phase 1b trial, avelumab had a response rate of 16 percent in a cohort of patients with mUC, including one complete response and six partial responses. Under the Prescription Drug User Fee Act, the FDA will make a final approval decision on the BLA on or before Aug. 27, 2017.

"Taken together with last year's filing for metastatic Merkel cell carcinoma, this BLA acceptance confirms our rapid and continued progress in the clinical development of avelumab," Luciano Rossetti, M.D., executive vice president, Global Head of Research & Development at the biopharma business of Merck KGaA, said in a statement. "We continue to evaluate avelumab in cancers that have limited or suboptimal treatment choices, such as metastatic or locally advanced urothelial carcinoma, to hopefully be able to provide patients with new treatment options for fighting their disease."

The phase 1b avelumab study included 44 patients with histologically or cytologically confirmed metastatic urothelial cancer that progressed after at least one platinum-containing regimen for unresectable or recurrent disease as well as patients who were cisplatin-ineligible. They received avelumab at a dose of 10 mg/kg as a one-hour IV infusion every two weeks. Patients were not preselected for PD-L1 expression. Treatment was continued until progression, unacceptable toxicity, or any criterion for withdrawal occurred.

The median duration of treatment was 13 weeks, and the median number of doses administered was 6.5. Median follow-up was 3.5 months. Sixteen patients remained on treatment.

There were seven responses (15.9 percent) by RECIST criteria. The median duration of response was not reached, and six of the seven responses were ongoing at the time of data analysis.

The proportion of patients alive and free of progression at 12 weeks was 47.2 percent. Eight patients (18.2 percent) had tumor shrinkage of at least 30 percent, including in patients with visceral metastasis.

Clinical activity was associated with PD-L1 expression. The objective response rate was 40 percent (4/10) in PD-L1­—positive patients (using a greater than 5 percent cutoff) compared with 9.1 percent (2/22) in PD-L1­­–negative patients.

The most common treatment-emergent adverse events with avelumab were infusion-related reactions, fatigue, nausea, asthenia, pyrexia, diarrhea and pruritus. Overall, 59.1 percent had treatment-emergent adverse events, with most being grade 1 or grade 2.

The ongoing phase 3 JAVELIN Bladder 100 trial (NCT02603432) is evaluating avelumab in the first-line setting as a maintenance treatment in patients with locally advanced or mUC.

"Advanced urothelial carcinoma remains a difficult-to-treat tumor, which is why we are developing a comprehensive clinical development program that involves phase 1 and 3 trials designed to address this challenge," Chris Boshoff, M.D., Ph.D., senior vice president and head of Immuno-oncology, Early Development and Translational Oncology, Pfizer Global Product Development, said in a statement. "We're continuing to accelerate our urothelial carcinoma development program and look forward to continuing our dialogue with the FDA."

In November 2016, the FDA granted a priority review to a BLA for avelumab for use as a treatment for patients with metastatic Merkel cell carcinoma.