Avelumab* is a fully human IgG1 antibody that inhibits PD-L1. In a large phase 1b study (NCT01772004), avelumab showed preliminary safety and efficacy in a cohort of 44 patients (pts) with metastatic urothelial carcinoma (mUC) progressed after platinum-based chemotherapy or platinum ineligible. An additional cohort was enrolled to further characterise efficacy and safety of avelumab in mUC.
Eligible pts received avelumab 10 mg/kg (1h IV infusion) Q2W until confirmed progression, unacceptable toxicity, or withdrawal. Tumours were assessed every 6 wks (RECIST 1.1) and reviewed by an independent committee. Confirmed objective response rate (ORR) and progression-free survival (PFS) were evaluated. Adverse events (AEs) were graded by NCI-CTCAE v4.0.
As of Jan 18, 2016, 129 pts were treated with avelumab, including 113 (87.6%) with disease progression after platinum-based therapy and 9 (7.0%) who were platinum ineligible. Primary tumour sites were bladder (74 pts, 57.4%), urethra (23 pts, 17.8%), renal pelvis (22 pts, 17.1%), or ureter (8 pts, 6.2%). Median time from metastatic diagnosis was 10.7 mos. Pts had received a median of 2 prior lines (range, 0-6) for advanced disease. Median duration of treatment was 10.4 wks (range, 2-36). 78 pts (60.5%) had a treatment-related (TR) AE; most common (≥10%) were infusion-related reaction (29 pts [22.5%]) and fatigue (19 pts [14.7%]). 9 pts (7.0%) had grade 3-4 TRAEs, of which only fatigue (2 pts [1.6%]) occurred in >1 pt. There was 1 treatment-related death (pneumonitis). Among 109 pts with ≥4 mos follow-up, confirmed ORR was 16.5% (95% CI: 10.1, 24.8) with 3 complete responses and 15 partial responses; 17/18 ongoing (94.4%). 21 pts (19.3%) had stable disease. Median PFS was 6.1 wks (95% CI: 6.0, 8.3) and PFS rate at 12 wks was 35.6% (95% CI: 26.5, 44.7).
Avelumab showed promising efficacy with durable responses and a manageable safety profile in pts with mUC who were platinum ineligible or progressed after platinum chemotherapy, confirming previous findings. Enrolment of 200 pts is planned. PD-L1 expression analysis is ongoing, as is a randomised phase 3 trial in mUC. *Proposed INN.
Clinical trial identification
Legal entity responsible for the study
EMD Serono, Inc. and Merck KGaA
J. Ellerton: Research Funding: Merck. M. Gordon: Research Funding: Merck Serono. K-W. Lee: Research Funding: Merck Serono, AstraZeneca, Taiho, Roche, and Ono Pharmaceuticals. J. Infante: Consulting or Advisory Role and Research Funding: EMD Serono. M. Schlichting: Employment: Merck KGaA, Darmstadt, Germany. K. Chin: Employment and Research Funding: EMD Serono Stock or Other Ownership: Bristol-Myers Squibb. All other authors have declared no conflicts of interest.