ASCO GU 2018: Preliminary results from patients with urothelial carcinoma in a phase 1A/1B study of bgb-A317, an anti-PD-1 monoclonal antibody

San Francisco, CA (UroToday.com)  Immune checkpoint inhibitors (ICI) continue to be tested in all different cancers in all different stages. In general, when success is identified, objective response rates seem to be about 15-20% of the population, but many of these patients have a durable response. Bladder cancer has been no exception, and there has been a great deal of success in the metastatic bladder cancer space. 

As our understanding of immune checkpoints continue to improve, there are more and more targetable pathways and actionable targets. While the PD-1/PD-L1/PD-L2 and CTLA-4 pathways predominate, there are some smaller pathways that are gaining attention. 

BGB-A317 is a humanized IgG4 monoclonal antibody (mAb) with high affinity and binding specificity for PD-1. Previous reports from an ongoing Phase 1A/1B study (NCT02407990) in patients with advanced solid tumors suggested that BGB-A317 was generally well tolerated and had antitumor activity in multiple tumor types. 

In this abstract, the authors from Australia present the preliminary results from a subset of patients with UC (urothelial carcinoma) enrolled in this study. As with many of the ICI studies in bladder cancer, only patients with metastatic bladder cancer. 

Patients with UC received intravenous BGB-A317 at doses of 2, 5, 10 mg/kg every 2-3 weeks and 200 mg every 3 weeks. Tumor cell (TC) and immune cell (IC) PD-L1 expression was retrospectively assessed with the VENTANA PD-L1 (SP263) assay. Safety and tolerability was assessed by monitoring adverse events (AEs) and antitumor effects were assessed by RECIST v1.1 criteria.

As of 8 June 2017, 15 patients with UC (median age, 72 yr [range: 39–79]) received BGB-A317 during phases 1A (n = 8) and 1B (n = 7). All patients were Caucasian and 13 patients were male; the median number of prior systemic anticancer therapies was 1 (range: 0–4). Median duration of treatment was 115 d (range: 27–476); 6 patients remain on treatment. 

In terms of safety, the most common treatment-related AEs (TRAEs) were fatigue (n = 5) and rash (n = 3); grade ≥3 TRAEs included fatigue (n = 1), and hyperglycemia and type 1 diabetes mellitus (T1DM; n = 1). Serious TRAEs occurred in 2 patients (infusion-related reaction [n = 1]; hyperglycemia and T1DM [n = 1]). 

In terms of preliminary efficacy data, all patients were evaluable for response assessment. Confirmed complete and partial responses occurred in 1 and 3 patients, respectively, for a response rate of 27%; the disease control rate (CR+PR+SD) was 53%. These are similar to other ICI studies in UC. 

From an immunohistochemistry standpoint, 9 samples were available for PD-L1 evaluation. Responses were observed in 3 of 6 patients with PD-L1+ tumors (defined as ≥25% TC or IC expressing PD-L1 by IHC) while 1 in 3 patients with PD-L1– tumors responded.

BGB-A317 was generally well tolerated in patients with UC and objective responses were observed in both PD-L1+ and PD-L1– diseases. BGB-A317 is currently being investigated in China as monotherapy for patients with PD-L1+ UC (CTR20170071).

Presented by: Shahneen Sandhu, MD
Co-Authors: Kaur Sandhu, Andrew Graham Hill, Hui Kong Gan, Michael Friedlander, Mark Voskoboynik, Paula Barlow, Amanda Rose Townsend, James Song, Yun Zhang, Zhirong Shen, Qinzhou Qi, Jayesh Desai

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Twitter: @tchandra_uromd at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA
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