Dual immunotherapy regimen shows early promise in urothelial carcinoma


Dual immune checkpoint blockade with the PD-1 inhibitor tislelizumab and the PD-L1 inhibitor BGB-A333 showed clinical activity in bladder cancer.

Dual immune checkpoint blockade with the PD-1 inhibitor tislelizumab and the PD-L1 inhibitor BGB-A333 induced an overall response rate (ORR) of 42% in a small study of patients with urothelial carcinoma.1

The findings showed that among 12 patients receiving the immunotherapy combination, there were 3 complete responses (CRs), and 2 partial responses (PRs). Another 4 patients achieved table disease, with 2 patients having progressive disease, and 1 patient not being evaluable. The median duration of response was 9.1 months. The ORR hit 67% (2 CRs; 2 PRs) among the subgroup of patients with PD-L1–high tumors. Among those with PD-L1–low tumors, the ORR was 17%.

“Simultaneous PD-L1 and PD-1 blockade has been hypothesized to provide synergistic antitumor effects, as inhibitors may have distinct mechanisms of action,” said lead study author Juan Martin-Liberal, MD, PhD, a consultant medical oncologist in the Melanoma, Sarcoma, and Genitourinary Tumors Unit at the Institut Catala d’Oncologia Hospitalet, in Barcelona, Spain, said when presenting the data during the 2020 ESMO Virtual Congress. “[Although] these differences should be taken cautiously given the sample size, these data have provided insights into combining tislelizumab, a clinical stage anti–PD-1 antibody, with anti–PD-L1 antibodies.”

Martin-Liberal shared data from the phase 2B portion of the phase 1/2 BGB-900-101 study. Patients had locally advanced or metastatic urothelial carcinoma that had progressed after at least 1 platinum-containing regimen. Patients had a median age of 69.5 years, and 92% of patients were male. Ten patients had received 1 prior line of systemic therapy. PD-L1–high status was defined as PD-L1 staining on 25% or more of tumor or immune cells with the VENTANA SP263 assay.

Patients received 1350 mg of intravenous (IV) BGB-A333 and 200 mg of IV tislelizumab every 3 weeks. The median treatment duration was 6.2 months and the median follow-up was 10 months.

The disease control rate (DCR) varied based on PD-L1 status. In the overall patient population, the DCR was 75%. In PD-L1–high patients, the DCR was 100% compared with 50% in PD-L1–low patients.

In the overall population, the median progression-free survival (PFS) was 6.1 months. In the PD-L1–high subgroup, the median PFS was 10 months compared with 4.1 months in the PD-L1–low subgroup.

Safety was evaluated in 39 patients, which included patients from phase 1 of the trial. Treatment-related adverse effects (TRAEs) across all grades occurred in 20 patients, with the most common being fatigue (n = 5), maculopapular rash (n = 4), myalgia (n = 4), nausea (n = 4), pruritis (n = 3), asthenia (n = 2), back pain (n = 2), and diarrhea (n = 2). A total of 7 patients experienced a grade 3 or higher TRAE, including 1 report of fatigue and 1 report of maculopapular rash.

Two patients in the phase 2B portion of the study experienced immune-related AEs, which consisted of grade 3 endocrine disorders, grade 3 hypophysitis, grade 2 musculoskeletal and connective tissue disorder, and grade 2 myositis. There were no patient deaths related to study treatment.


1. Martin-Liberal H, Fong P, Moreno V, et al. BGB-A333, an anti-PD-L1 monoclonal antibody, in combination with tislelizumab in patients with urothelial carcinoma. Ann Oncol. 2020;31(4). Abstract: 535MO.

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