Updated efficacy and safety of avelumab in metastatic urothelial carcinoma (mUC): Pooled analysis from 2 cohorts of the phase 1b Javelin solid tumor study.

Abstract

4528 Background: Avelumab, a fully human anti‒PD-L1 IgG1 antibody, has shown promising efficacy and safety in 2 cohorts of patients (pts) with mUC. We now report updated data from a pooled analysis of these pts with mUC from JAVELIN Solid Tumor (NCT01772004) and further characterize the clinical activity of avelumab in this disease. Methods: Pts with mUC progressed after platinum-based therapy or cisplatin ineligible received avelumab 10 mg/kg 1-hour IV Q2W. Tumors were assessed every 6 weeks by independent review (RECIST v1.1). Endpoints included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety (NCI CTCAE v4.0), and tumor PD-L1 expression. Results: As of Jun 9, 2016, 249 pts had received avelumab for a median of 12 weeks (range 2-92) and were followed up for a minimum of 6 weeks. Primary tumor site was upper tract (renal pelvis/ureter) in 23.3% and lower tract (bladder/urethra) in 76.7%. 242 pts (97.2%) had progressed on prior platinum therapy and 7 pts (2.8%) were platinum naive. In 161 post-platinum pts with ≥6 months of follow-up, confirmed ORR was 17.4% (95% CI 11.9-24.1; complete response in 6.2%) with a disease control rate of 39.8%. Response was ongoing in 23/28 responders at data cut (82.1%; median DOR not reached), and the 24-week durable response rate was 92.3% (95% CI 72.6-98.0). Responses occurred across PD-L1 expression levels tested (≥5% and < 5% tumor cell‒staining [25.4% and 13.2%]). In all post-platinum pts (n = 242), median PFS was 6.6 weeks (95% CI 6.1-11.6), median OS was 7.4 months (95% CI 5.7-10.3) and 6-month OS rate was 54.9 (95% CI 47.7-61.7). Treatment-related adverse events (TRAE) of any grade occurred in 166/249 pts (66.7%); most common (≥10%) were infusion-related reaction (22.9%, all grade ≤2) and fatigue (16.1%). 21 pts (8.4%) had a grade ≥3 TRAE (fatigue [1.6%] and asthenia [0.8%] in > 1 pt). 34 pts (13.7%) had an immune-related AE (grade ≥3 in 2.4%). There was 1 treatment-related death (pneumonitis). Conclusions: Avelumab was well tolerated and showed durable responses in heavily pretreated pts with mUC, irrespective of tumor PD-L1 expression status. Clinical trial information: NCT01772004.