Instant Report

Date: 10-Jun-2021

China NMPA Accepts BeiGenes SBLA For Tislelizumab To Treat Locally MSI-H Or DMMR Solid Tumors

BeiGene, a global biotechnology company, announced that the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) has accepted a supplemental Biologics License Application (sBLA) for anti-PD-1 antibody tislelizumab for the treatment of patients with previously treated, locally advanced unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumors.

“We are excited by the acceptance of our filing for tislelizumab in patients with MSI-H or dMMR solid tumors, which underscores our ongoing commitment to pursuing the full potential of tislelizumab, a potentially differentiated checkpoint inhibitor, and expanding its access where there is unmet medical need. This submission also marks the seventh indication submitted to health authorities, including three approvals for our tislelizumab program,” commented Yong (Ben) Ben, M.D., chief medical officer, Immuno-Oncology at BeiGene. “Results from our phase 2 trial demonstrated that tislelizumab’s treatment effect was consistent and durable across tumor types and endpoints. We are encouraged by the data and plan to continue our communications with the CDE, hoping to bring this medicine to more patients.”

The sBLA is supported by clinical results from a single-arm, multi-center, open-label; pivotal phase 2 clinical trial (NCT03736889) to evaluate efficacy and safety of tislelizumab as monotherapy in patients with previously treated locally advanced unresectable or metastatic MSI-H or dMMR solid tumors, with an enrollment of 80 patients in China. Patients received tislelizumab 200 mg intravenously every three weeks until disease progression, unacceptable toxicity, or withdrawal. Radiological imaging was performed at nine weeks and then every six weeks for the first year of therapy and every 12 weeks thereafter. The primary efficacy analysis set included patients who received any dose of tislelizumab with measurable disease per independent review committee (IRC) at baseline. The primary endpoint of this trial is objective response rate (ORR) as assessed by IRC per RECIST v1.1; secondary endpoints include time to response (TTR), duration of response (DoR), disease control rate (DCR), and progression-free survival (PFS) as assessed by investigator and IRC, overall survival (OS), and safety and tolerability.

Microsatellite instability-high (MSI-H) cancer cells have a greater than normal number of genetic markers called microsatellites, which are short, repeated sequences of DNA. Cancer cells that have large numbers of microsatellites may have defects in the ability to correct mistakes (also known as mismatch repair deficiency, or dMMR) that occur when DNA is copied in the cell. MSI-H and dMMR tumors are found most often in colorectal cancer and other types of gastrointestinal cancer and endometrial cancer, although they may also be found in cancers of the breast, prostate, bladder and thyroid.

Tislelizumab (BGB-A317) is a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to Fc?R on macrophages. In pre-clinical studies, binding to Fc?R 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 from BeiGene’s immuno-oncology biologics program and is being developed internationally as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers.