More Than Half of Urothelial Cancer Patients Benefited from Tislelizumab in a Phase 1 Trial

More Than Half of Urothelial Cancer Patients Benefited from Tislelizumab in a Phase 1 Trial

BeiGene‘s investigational antibody tislelizumab was well-tolerated and induced at least stable disease in 53 percent of urothelial carcinoma patients treated in a Phase 1a/b clinical trial.

The data was presented recently in a poster, “Preliminary results from patients with urothelial carcinoma (UC) in a phase 1A/1B study of bgb-A317, an anti-PD-1 monoclonal antibody,” at the 2018 Genitourinary Cancers Symposium, Feb. 8-10, San Francisco.

Tumors use several strategies to evade an immune response. One of them is increasing the expression of a protein, called programmed death-ligand 1 (PD-L1), that binds a receptor in immune cells — the so-called programmed cell death-1 (PD-1) — acting as an “off switch” for the immune response.

Inhibitors of PD-1 are a strategy widely used in cancer therapeutics to reactivate the immune system to attack tumors.

Tislelizumab (also known as BGB-A317) is a monoclonal antibody targeting PD-1 and its effectiveness is being tested in a Phase 1 clinical trial (NCT02407990) in 451 patients with several types of advanced cancers.

One of the trial groups included 16 patients with urothelial carcinoma. The majority (12 patients) had been treated previously with anti-cancer therapies and four experienced disease progression after receiving chemotherapy as a main or secondary treatment.

Early results from 15 patients who received tislelizumab for a median of 4.3 months (range of 0.7 to 18.3 months) showed that 27 percent responded to the therapy. One patient achieved a complete response, meaning there were no signs of cancer, and three patients saw a reduction in the tumor size (partial response).

Additionally, four patients had their disease stabilized by the treatment, meaning 53 percent of patients had some sort of benefit from tislelizumab. Six patients remain on treatment.

Patients with high PD-L1 expression in their tumors had better responses to the treatment, researchers found. Indeed, all six patients with high PD-L1 benefited from tislelizumab — one complete response, two partial responses, and one stable disease — while only one partial response was observed among the three patients who were either low-expressing or negative.

The adverse effects were mild (grade 1 or 2) and included fatigue, rash, infusion related reactions, nausea, pain in extremity, and proteinuria (high protein levels in the urine).

“Tislelizumab administration resulted in objective responses, including a complete response, and a disease-control rate of 53 percent. Tislelizumab was generally well-tolerated in patients with urothelial carcinoma,” study lead author Shahneen Sandhu, MD, said in a press release. Sandhu is a medical oncologist at the Peter MacCallum Cancer Center in Melbourne, Australia.

“We are highly encouraged by these results and that further study of tislelizumab may lead to a new treatment for patients with urothelial cancer,” Sandhu added.

“This is the first presentation of tislelizumab data in the population with urothelial cancer, an area of unmet need,” said Amy Peterson, MD, chief medical officer, Immuno-Oncology, at BeiGene. “We are pleased by these preliminary results, which we believe provide an important foundation for our clinical understanding of tislelizumab’s efficacy and safety in specific patient populations both as a single agent and in combination.”