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Tislelizumab impresses in Phase 2 trial
BEIJING & CAMBRIDGE, Mass.—A recent trial provided positive top-line results for BeiGene Ltd. after an independent review of the data from its pivotal Phase 2 trial of tislelizumab in Chinese patients with relapsed/refractory classical Hodgkin's lymphoma (cHL).
The trial in question was a Phase 2, single-arm pivotal trial of tislelizumab in 70 patients with cHL who either failed autologous stem cell transplantation or were ineligible for such treatment. The trial's primary endpoint was overall response rate (ORR), with secondary endpoints consisting of progression-free survival (PFS), duration of response (DOR), complete response (CR) rate, time to response, safety and tolerability.
Tislelizumab is an investigational humanized monoclonal antibody, an immune checkpoint inhibitor that binds to PD-1 with high affinity and specificity. While there are a multitude of PD-1 inhibitors in the clinic and on the market, BeiGene points out that tislelizumab 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.”
An independent review committee looked at patient responses to tislelizumab and found that ORR was 73 percent, with a CR rate of 50 percent. As of the data cutoff, with patients having been followed an average of six months, median DOR had not been reached.
In terms of adverse events, their frequency and severity were largely in line with tislelizumab's previously reported Phase 1 safety and tolerability data. While some immune-related events occurred (fever and hypothyroidism), they were consistent with results seen from other PD-1 antibodies administered to cHL patients.
“We are excited to announce the preliminary top-line results from our first pivotal trial for tislelizumab. Despite short follow-up, we believe there was a demonstration of robust activity, with high overall and complete response rates in addition to a safety profile that is consistent with other PD-1 inhibitors. We believe these strong results will support our first regulatory filing in China for tislelizumab, which is planned for later this year,” Dr. Jane Huang, BeiGene's chief medical officer, Hematology, said in a press release.
Global Phase 3 trials of tislelizumab are also underway in indications such as second-line non-small cell lung cancer, hepatocellular carcinoma and esophageal squamous cell carcinoma. Two Phase 2 trials are also being conducting in patients with previously treated hepatocellular carcinoma or with relapsed/refractory mature T and NK-cell lymphomas, as is a pivotal Phase 2 trial in China in urothelial cancer.
BeiGene shared news on July 24 that it had dosed the first patient in a Phase 3 trial of tislelizumab in combination with chemotherapy as a potential first-line treatment for patients with stage IIIB or IV non-squamous non-small cell lung cancer (NSCLC). This study will be an open-label, multi-center trial that will enroll roughly 320 chemotherapy-naive patients in mainland China. The primary focus will be PFS as determined by an independent review committee, with secondary endpoints including overall survival, ORR, PFS by investigator and safety/tolerability.
“We are pleased to be enrolling patients in this important trial evaluating the potential impact of adding tislelizumab, an investigational immuno-oncology therapy, to platinum plus pemetrexed chemotherapy, the current global standard of care in first-line treatment of patients with advanced-stage non-squamous NSCLC,” remarked Dr. Amy Peterson, chief medical officer for Immuno-Oncology at BeiGene.
BeiGene likely isn't the only one pleased by this recent news, as it and Celgene Corporation are collaborating on the development and commercialization of tislelizumab. The companies began a strategic collaboration in July 2017, with a focus on solid tumor cancers in the United States, Europe, Japan and the rest of the world outside of Asia. The agreement stipulated that BeiGene will hold onto exclusive rights for developing and commercializing tislelizumab for hematological malignancies globally and for solid tumors in Asia (excluding Japan). In addition, BeiGene will acquire Celgene's commercial operations in China and secure an exclusive license to commercialize Abraxane, Revlimid and Vidaza, Celgene's therapies that are approved in China.
In terms of financials, the collaboration includes upfront licensing fees paid to BeiGene of $263 million, with the potential for as much as $980 million in development, regulatory and sales milestones. Additionally, Celgene agreed to acquire an equity stake in BeiGene through the purchase of 32.7 million (5.9 percent) of the latter's ordinary shares are $4.58 per share.