Tislelizumab (BGB-A317) is a humanized IgG4 anti–PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages. In pre-clinical studies, binding to FcγR on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells. Tislelizumab is the first drug candidate produced from BeiGene’s immuno-oncology biologic program, and we believe it could serve as a key element of our immuno-oncology combination platform. Tislelizumab is being developed as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers.

Mechanism of Action

Tislelizumab was designed to bind to PD‑1, a cell surface receptor that plays an important role in allowing tumor cells to evade the immune system. Many types of cancer cells have hijacked the PD‑L1 expression system that normally exists in healthy cells. By expressing PD‑L1, cancer cells can interact with PD‑1 expressing cytotoxic T‑lymphocytes, or CTLs and protect themselves from being killed by these CTLs. Tislelizumab can potentially restore the ability of CTLs to kill cancer cells by binding to PD‑1, without activating the receptor, thereby preventing PD‑L1 from engaging PD‑1.

Tislelizumab Clinical Trials

Tislelizumab is in pivotal Phase 3 and Phase 2 clinical trials in solid tumors and hematologic cancers, including a pivotal Phase 2 clinical trial in relapsed/refractory classical Hodgkin’s lymphoma (R/R cHL). It is also being studied in global Phase 3 trials in a number of malignancies, including non-small cell lung cancer, hepatocellular carcinoma, and esophageal squamous cell carcinoma, as well as two global Phase 2 trials in patients with previously treated hepatocellular carcinoma or with R/R mature T- and NK-cell lymphomas, and an additional pivotal Phase 2 trial in China in urothelial cancer.

For more clinical trial information please visit: Clinicaltrials.gov.

Tislelizumab Monotherapy Trials

Tislelizumab, as a monotherapy, is in pivotal Phase 3 clinical trials globally in second-line non-small cell lung cancer, first-line hepatocellular carcinoma (HCC), and second-line esophageal carcinoma. It is also being studied as a monotherapy in pivotal Phase 2 clinical trials in relapsed/refractory classical Hodgkin’s lymphoma (R/R cHL), second-line urothelial carcinoma, and second- or third-line HCC. It is also in a Phase 2 clinical trial as a monotherapy in R/R NK/T-cell lymphoma.

Tislelizumab Combinations

In Combination with Chemotherapy

In certain solid tumors, such as NSCLC, immune checkpoint inhibitors have been shown to provide benefit when combined with standard chemotherapy regimens. We are evaluating tislelizumab in combination with chemotherapy in global Phase 3 trials in first‑line gastric cancer and first-line esophageal cancer, and in China in first-line NSCLC. 

In Combination with Pamiparib

Pamiparib (BGB-290) is an investigational small molecule inhibitor of PARP1 and PARP2. In a multi‑center, Phase 1b trial, BeiGene is evaluating pamiparib combined with tislelizumab for a variety of solid tumor malignancies. 

In Combination with Zanubrutinib

Zanubrutinib (BGB-3111) is a small molecule inhibitor of Bruton’s tyrosine kinase, or BTK, that is currently being evaluated in a broad pivotal clinical program globally and in China as a monotherapy and in combination with other therapies to treat various lymphomas. We are also evaluating zanubrutinib in combination with tislelizumab in an open-label, multi‑center Phase 1b trial.