Avelumab Granted Priority Review by FDA for Metastatic Urothelial Carcinoma

A biologics license application for avelumab has been granted a priority review by the FDA for the treatment of patients with locally advanced or metastatic urothelial carcinoma.

Luciano Rossetti, MD

Luciano Rossetti, MD

A biologics license application (BLA) for avelumab has been granted a priority review by the FDA for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) whose disease has 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 Ib trial, avelumab had a response rate of 16% in a cohort of patients with mUC, including 1 complete response and 6 partial responses. Under the Prescription Drug User Fee Act, the FDA will make a final approval decision on the BLA on or before August 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, MD, 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 Ib avelumab study included 44 patients with histologically or cytologically confirmed metastatic urothelial cancer that progressed after at least 1 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 1-hour IV infusion every 2 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 7 responses (15.9%) by RECIST criteria. The median duration of response was not reached, and 6 of the 7 responses were ongoing at the time of data analysis.

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

Clinical activity was associated with PD-L1 expression. The objective response rate was 40% (4/10) in PD-L1­—positive patients (using a ≥5% cutoff) compared with 9.1% (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% had treatment-emergent adverse events, with most being grade 1 or grade 2.

The ongoing phase III 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 I and III trials designed to address this challenge," Chris Boshoff, MD, PhD, 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.


Apolo AB, Infante JR, Hamid O, et al. Safety, clinical activity, and PD-L1 expression of avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with metastatic urothelial carcinoma from the JAVELIN Solid Tumor phase Ib trial.J Clin Oncol.2016;34 (suppl 2S; abstr 367).

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