BeiGene Presents Encouraging Results in Ph I Trial of Tislelizumab in Patients with Microsatellite Instability-High or Mismatch Repair-Deficient Solid Tumors

• The objective response rate was 29 percent (4 of 22 patients)
• BeiGene and Celgene Corporation have a global strategic collaboration for the development of tislelizumab in solid tumor cancers outside of Asia
• Tislelizumab is also in Ph II and Ph III trials in other cancer types

BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), on 9/20/18 presented preliminary clinical data from Chinese patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumors enrolled in an ongoing Phase 1/2 clinical trial of tislelizumab, an investigational anti-PD-1 antibody, at the 21st Annual Meeting of the Chinese Society of Clinical Oncology (CSCO) in Xiamen, China.

“Tislelizumab is being developed in a broad clinical program as both a monotherapy and in combination with other treatments for a number of potential clinical indications. We are encouraged by the preliminary results presented today with tislelizumab for patients with MSI-H or dMMR solid tumors and are excited about starting a Phase 2 trial in China in patients with advanced forms of these tumors to test our belief that they are sensitive to immune checkpoint inhibition. We hope this further enables the availability of new treatments options, which are urgently needed, especially in China,” commented Amy Peterson, M.D., Chief Medical Officer, Immuno-Oncology, at BeiGene.

“This is the first presentation of tislelizumab data in the population of patients with MSI-H or dMMR solid tumors, and we are encouraged by the objective response rate of 29 percent in a difficult-to-treat patient population. Tislelizumab was also generally well-tolerated in these patients,” said Lin Shen, M.D., Vice President of Clinical Oncology at Beijing Cancer Hospital and Peking University, and study presenter. “We hope that further study of tislelizumab may lead to a new treatment for patients with these tumors.”

The multi-center, open-label Phase 1/2 trial of tislelizumab as monotherapy in advanced solid tumors in China (CTR20160872) consists of a Phase 1 dose verification component and a Phase 2 component of indication expansion in disease-specific cohorts, which includes MSI-H and dMMR solid tumors.
Data presented at CSCO today are from 22 patients enrolled in the cohort, of which 14 patients with centrally confirmed MSI-H/dMMR tumors were evaluable for antitumor activity per RECIST v1.1 criteria. Patients were treated with tislelizumab at a dose of 200 mg every three weeks. Colorectal cancer was the most common primary tumor type and 82 percent of the study population received one or more prior lines of systemic therapy. At the time of the data cutoff on May 11, 2018, median treatment duration was 2.2 months (0.69-11.1 months), median follow-up time was 4.4 months (0.10-10.7 months), and ten patients remained on treatment.

Adverse events (AEs) assessed by the investigator to be related to treatment occurred in 18 patients (82%). Of those, the most common treatment-related AEs (TRAEs) (occurring in ≥ 15% of patients) were increased bilirubin (36%), increased transaminase (27%), increased blood creatine phosphokinase (23%), anemia (23%) and decreased white blood cell and/or neutrophil count (18%). All of the TRAEs were grades 1 or 2. Immune-related AEs (irAEs) occurred in 13 patients (59%) and many were overlapping with the TRAE cases. All irAEs were grade 1 or 2 as well.

At the time of the data cutoff, the efficacy evaluation was early and 14 patients, including 12 patients with colorectal cancer, with centrally confirmed MSI-H/dMMR tumors were evaluable for response. The objective response rate was 29 percent (four patients, all with colorectal cancer), with the median duration of response still maturing. Additionally, three patients centrally confirmed as negative for MSI-H/dMMR were evaluable for response, and progressive disease was the best response in all three of these patients.

In addition to this Phase 1/2 trial, tislelizumab is being investigated in two pivotal Phase 2 clinical trials in China in relapsed/refractory (R/R) classical Hodgkin’s lymphoma and in urothelial cancer, Phase 3 trials in China and globally 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.

Tislelizumab (BGB-A317) is an investigational humanized monoclonal antibody that belongs to a class of immuno-oncology agents known as immune checkpoint inhibitors. Discovered by BeiGene scientists in Beijing, tislelizumab is designed to bind to PD-1, a cell surface receptor that plays an important role in downregulating the immune system by preventing the activation of T-cells. Tislelizumab has demonstrated high affinity and specificity for PD-1. It is potentially differentiated from the currently approved PD-1 antibodies in an engineered Fc region, which is believed to minimize potentially negative interactions with other immune cells, based on preclinical data.

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. BeiGene and Celgene Corporation have a global strategic collaboration for the development of tislelizumab in solid tumor cancers outside of Asia (except Japan).