HONG KONG – With an NDA for tislelizumab currently under review at the National Medical Products Agency (NMPA) for relapsed or refractory classical Hodgkin lymphoma, China biotech Beigene Ltd. started enrolling patients into two global phase III trials testing the PD-1-inhibiting antibody in gastric cancer and esophageal squamous cell carcinoma (ESCC).

Tislelizumab, a humanized IgG4 anti-PD-1 monoclonal antibody (MAb) seeking to minimize binding to FcyR on macrophages, is in development for a total of 10 indications as monotherapy and two combined with other drugs in Beigene's pipeline.

"We are working with our partner, Celgene Corp., to develop tislelizumab for solid tumors," Liza Heapes, Beigene's spokesperson, told BioWorld. "We retain solid rights to the molecule in Asia, excluding Japan. We retain hematologic rights to the molecule worldwide."

The phase III trial for gastric cancer is randomized, double-blind and placebo-controlled. The company plans to enroll a total of 720 patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma, a type of cancer of the esophagus, who will receive 200 mg of tislelizumab, or placebo, combined with platinum- and fluoropyrimidine-based chemotherapy – the standard chemotherapy treatment – once every three weeks. Progression-free survival and overall survival are the study's primary endpoints. Its secondary endpoints include overall response rate (ORR), duration of response and quality of life, as well as safety and tolerability.

The second study, in unresectable, locally advanced recurrent or metastatic ESCC, will use identical endpoints and design, with the total number of patients enrolled expected to be about 480.

"We will work as hard as possible to get them [the trials] finished as we know there are a lot of patients diagnosed with these diseases," Heapes said. Assuming positive data, the company "will consider applying for reimbursement for tislelizumab under the new drug regulation list [NDRL] program" after the NDAs for the two indications are approved, she added.

The company's NDA for tislelizumab targeting relapsed or refractory classical Hodgkin lymphoma (R/R cHL) was accepted by China's NMPA in August. Beigene presented the results from the indication's phase II study in Chinese patients, which showed an ORR of 85.7 percent in the 70 enrolled patients.

"The NMPA does not give a specific timeline for approval, but we have priority review status," Heapes said. "The NMPA has moved quickly in the past, approving the other PD-1-targeted therapies in about six months, but we have no guidance on when approval of tislelizumab may be given."

She added that the firm would potentially see its approval next year.

Also in August, the listed biotech company kicked off the open-label and multicenter phase III trial in China that combines the MAb with chemotherapy as a first-line treatment for patients with advanced squamous non-small-cell lung cancer (NSCLC). The trial is designed to enroll about 340 patients.

Since April, the Beijing-based drugmaker has been conducting the global phase II trial of tislelizumab for patients with relapsed or refractory mature T- and natural killer (NK)-cell lymphomas. The open-label and multicenter study is assessing the efficacy and safety of tislelizumab in about 90 patients from greater China, Italy, Germany, France and the U.S.

The molecule is also undergoing a multicenter global phase II trial in about 225 patients with previously treated advanced hepatocellular carcinoma (HCC) from greater China, the U.S. and Europe.

On top of targeting its potential as a first-line treatment for ESCC, tislelizumab is being evaluated for suitability as a second-line treatment. A randomized, open-label, multicenter global phase III trial was started in late January. It admitted about 450 patients from greater China, Japan, South Korea, the U.K., the U.S., Belgium, France, Germany, Italy and Spain.

Tislelizumab is also in two global phase III trials – as second-line treatment for NSCLC and first-line treatment for HCC. It is also in a global phase I trial for treating solid tumors.

In other, separate global phase I studies, tislelizumab is combined with pamiparib, an inhibitor of PARP1 and PARP2 enzymes, to target solid tumors, and is combined with zanubrutinib, a BTK inhibitor, seeking to treat hematological tumors.

Asked about Beigene's development strategy next year, Heapes said: "We are preparing for the launches [of tislelizumab and Zanubrutinib] by growing the capabilities of our commercial team. More broadly, 2019 will see more organizational growth and continued progress on our broad clinical program."

In Hong Kong trading on Thursday, shares of Beigene (HKG:6160) rose 2.4 percent to HK$80 (US$10.22). Its shares on Nasdaq (NASDAQ:BGNE) ended the day at 137.85.