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ESMO 2020

ESMO Virtual Congress 2020: BGB-A333, an Anti-PD-L1 Monoclonal Antibody, in Combination with Tislelizumab in Patients with Urothelial Carcinoma

(UroToday.com) Despite similar mechanisms of action, antibodies (such as nivolumab and pembrolizumab) against the T-cell checkpoint PD-1 protein have different safety and efficacy profiles when used in cancer therapy. This is likely due to in part to differences in antibody humanization, sequence differences in complementarity-determining regions, as well as different pharmacokinetics.1 While durable responses are observed in a subset of patients treated with these agents, further improvements in disease control in the context of immune checkpoint blockade are needed. It has been hypothesized that blocking both T-cell PD-1 as well as its ligands on tumor cells (PD-L1, PD-L2) could have synergistic antitumor effects. In this presentation, Dr. Juan Martin-Liberal shared data from the phase 2B dose expansion cohort of a clinical trial (NCT03379259) of the anti-PD-L1 antibody BGB-A333 in combination with the anti-PD-1 antibody tislelizumab in patients with advanced urothelial carcinoma who progressed after platinum therapy.


The schema of the trial to date is shown below. A phase 1 dose-escalation and confirmation cohort set the phase 2 dosing of BGB-A333 at 1350 mg IV every three weeks along with tislelizumab 200 mg IV every three weeks.

ESMO20_BGB-A333.png


Below are reported treatment-related adverse events for all 39 patients enrolled in the phases of this protocol. Fatigue was the most commonly noted event. Two patients in the phase 2B cohort experienced 4 immune-related adverse events (grade 3 endocrine disorder, grade 3 hypophysitis, grade 2 muscular/connective tissue disorder, and grade 2 myositis).

ESMO20_tislelizumab.png

The overall response rate in the phase 2B cohort was 42% (5/12 patients) with 3 complete responses. The median duration of response was 9.1 months. Three patients of the 12 continue to undergo treatment with this drug combination. Median progression-free survival was 6.1 months (range 1.9 – 11), with a longer median PFS noted in high PD-L1 expression (as measured by Ventana SP263 assay showing > 25% of tumor or immune cells expressing PD-L1) relative to low PD-L1 expression (10 months, range 4 – 11 versus 4.1 months, range 1.2 – 11.5).

ESMO20_Ventana.png



Dr. Martin-Liberal concluded that combination BGB-A333 and tislelizumab was generally well-tolerated and induced objective responses in a subset of patients treated with this combination, with a suggestion of improved efficacy in PD-L1-high tumors.

Of note, phase 2 data of tislelizumab as monotherapy for patients with PD-L1 positive (by Ventana SP263 IHC assay) advanced urothelial carcinoma progressing after platinum therapy was presented at ESMO 2019 (Abstract 2382). Of 104 evaluable patients in that cohort treated with 200 mg IV tislelizumab every three weeks, 24 patients (23%) had an objective response, including 8 complete responses. Median PFS and OS were 2.1 and 9.8 months. 

Presented by: Juan Martin-Liberal, MD, PhD, Medical Oncologist at the Catalan Institute of Oncology, Hospitalet, Barcelona, Spain

Written by: Alok Tewari, MD, PhD, Medical Oncologist at the Dana-Farber Cancer Institute, 2020 European Society for Medical Oncology Virtual Congress (#ESMO20), September 19th-September 21st, 2020.

References:

  1. Naing A, Infante J, Goel S, et al. Anti-PD-1 monoclonal antibody MEDI0680 in a phase I study of patients with advanced solid malignancies. Journal for ImmunoTherapy of Cancer 2019;7:225. doi: 10.1186/s40425-019-0665-2