Avelumab, a human anti–PD-L1 monoclonal antibody, has shown promising efficacy and safety in patients (pts) with mUC. We report an updated analysis of avelumab treatment in 2 cohorts of pts from JAVELIN Solid Tumor (NCT01772004).
Pts with mUC whose disease had progressed after platinum-based therapy or were cisplatin ineligible received avelumab 10 mg/kg 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), and safety (NCI CTCAE v4.0), and tumor PD-L1 expression. Kaplan-Meier (K-M) method was used to estimate DOR, PFS, and OS.
As of Sep 2016, 249 pts had received avelumab and were followed for ≥6 mos (median 13.6 mos); 43 pts (17.3%) remained on treatment. 13 pts (5.2%) were cisplatin ineligible, including 7 (2.8%) platinum naïve. Confirmed ORR in all pts (n = 249) was 17.3% (95% CI 12.8–22.5; complete response in 4.4%) and the disease control rate was 44.6%. Response was ongoing in 34/43 pts (79.1%), median DOR was 20.1 mos (95% CI 9.7–20.1) and the K-M estimate of DOR of 6 mos was 92.7% (95% CI 79.1–97.6). In evaluable pts (n = 206), ORR in PD-L1+ and PD-L1– subgroups (≥5% tumor cell cut-off) was 25.6% and 13.7%, respectively. Median PFS was 1.6 mos (95% CI 1.4–2.7), median OS was 8.2 mos (95% CI 6.3–10.8), and the K-M OS rate at 12 mos was 41.9% (95% CI 34.8–48.7). 170/249 pts (68.3%) had a treatment-related adverse event (TRAE) of any grade, most commonly infusion-related reaction (23.3%) and fatigue (17.3%). 26 pts (10.4%) had a grade ≥3 TRAE, most commonly fatigue (1.6%), elevated lipase (1.6%), and pneumonitis (1.2%). 43 pts (17.3%) had an immune-related AE (grade ≥3 in 3.6%). 8 pts (3.2%) discontinued avelumab due to a TRAE. There was 1 treatment-related death (pneumonitis).
Avelumab showed durable clinical activity and had a manageable and tolerable safety profile in pts with mUC irrespective of PD-L1 expression. A phase 3 trial of avelumab as maintenance therapy after first-line platinum-based therapy for advanced UC is ongoing.
Clinical trial identification
NCT: NCT01772004 Protocol number: EMR 100070-001
Legal entity responsible for the study
Pfizer Inc., New York, NY, USA and Merck KGaA, Darmstadt, Germany
Funding was provided by Pfizer Inc., New York, NY, USA and Merck KGaA, Darmstadt, Germany
J.R. Infante: Provided consulting to BioMed Valley Discoveries, Inc. and ARMO BioSciences. M.S. Gordon: Received research funding from EMD Serono and MedImmune. C.D. Britten: Institution has received grants/research support from EMD Serono Inc. and Pfizer Inc. Attended dinner meetings for EMD Serono. M.H. Taylor: Has been an advisor for Blueprint Medicines, and a consultant for Trillium Pharma, Bristol- Myers Squibb. Speaker’s Bureau for Eisai Inc. Received honoraria from Blueprint Medicines, Trillium pharma, Bristol-Myers Squibb, Eisai Inc. P. Schöffski: Honoraria (institutional support): Daiichi Sankyo, Eisai, Eli Lilly, Medpace, Novartis, Swedish Orphan Biovitrium. Consulting or advisory role (institutional support): 6th Element Capital, Adaptimmune, Amcure, AstraZeneca, Bayer, Blueprint Medicines, Boehringer lngelheim, Cristal Therapeutics, Daiichi Sankyo, Eisai, Eli Lilly, Medpace, Novartis, Philogen, Piqur Therapeutics. Consulting or advisory role (institutional): BMS, Epizyme, Genzyme, Ipsen, Loxo Oncology, Nektar, Plexxikon. Speaker\'s Bureau (institutional support): Bayer, Eisai, Eli Lilly, GSK, Novartis, PharmaMar, Swedish Orphan Biovitrium. Research Funding (institutional support): Bayer, Blueprint Medicines, Cobiores nv, Exelixis, GSK, Novartis, Plexxikon. Travel, accommodation, expenses (institutional support): 6th Element Capital, Adaptimmune, Amcure, AstraZeneca, Bayer Blueprint Medicines, Boehringer lngelheim, Cristal Therapeutics, Daiichi Sankyo, Eisai, Eli Lilly, GSK, Medpace. Novartis, PharmaMar, Philogen, Piqur Therapeutics, Swedish Orphan Biovitrium. Travel, accommodation, expenses (institutional): BMS, Epizyme, Genzyme, Ipsen, Loxo Oncology, Nektar, Plexxikon. A. Gelb: Employee of EMD Serono Inc. A.G holds stock in Halozyme Therapeutics. J. Xiong, G. Rosen: Employee of EMD Serono Inc. M.R. Patel: Advisory/Board Member: Guardant. Speaker’s Bureau: Exelixis, Bristol-Myers Squib, Medivation, Genentech and Gilead. All other authors have declared no conflicts of interest.