Phase III Trial of Anti-PD-1 Antibody Tislelizumab + Chemotherapy Initiated as Treatment for NSCLC

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BeiGene, a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs, has dosed the first patient dosed in a Phase III clinical trial of tislelizumab, also known as BGB-A317,an investigational anti-PD-1 antibody, combined with chemotherapy, as a potential first-line treatment in China for patients with Stage IIIB or IV squamous non-small cell lung cancer (NSCLC).

In China, there were an estimated 733,300 new cases of lung cancer in 2015.[1] Lung cancer is the leading cause of cancer-related death in both men and women, with an estimated 610,200 deaths in China in 2015.[1] According to the American Cancer Society, about 80 to 85% of lung cancers are non-small cell lung cancer (NSCLC) and there are three main subtypes: adenocarcinoma, squamous cell (epidermoid) carcinoma and large cell (undifferentiated). For patients with advanced NSCLC, five-year survival rates are approximately 26 percent for Stage IIIB, 10% for Stage IVA, and 1 percent for Stage IVB.[2]

Tislelizumab
The investigational humanized monoclonal antibody tislelizumab 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).

Research
Tislelizumab is also being studied in global Phase III trials in solid tumors, including second-line NSCLC, first-line hepatocellular carcinoma, and second-line esophageal squamous cell carcinoma; two global Phase II trials in previously treated advanced hepatocellular carcinoma and relapsed/refractory mature T- and natural killer-cell lymphomas; a Phase III trial in China in non-squamous NSCLC; and two pivotal Phase II trials in China in relapsed/refractory classical Hodgkin’s lymphoma and second-line urothelial cancer.

Important trial
“With the start of this important Phase III trial in China for patients with squamous NSCLC, our broad development program for tislelizumab, an advanced immuno-oncology therapy, continues to make great progress in China and globally,” noted Amy Peterson, M.D., Chief Medical Officer for Immuno-Oncology at BeiGene.

“More than 1,500 patients have been enrolled in clinical trials with tislelizumab over the past three years, and we are excited to evaluate its potential when combined with both paclitaxel and carboplatin, the worldwide standard of care, or nab-paclitaxel (ABRAXANE®) and carboplatin, a newer regimen which has not yet gained approval in China but is approved in other geographies,” Peterson added.

Outcomes
“Despite some recent developments, available data indicate that outcomes in patients with squamous NSCLC may be worse than those in patients with other forms of lung cancer. As shown by most recent data with other checkpoint inhibitors, combining immunotherapy and chemotherapy consisting of platinum and paclitaxel or nab-paclitaxel improves anti-tumor activity and significantly improves outcomes for patients with advanced squamous NSCLC. This Phase III study, in addition to our Phase III first line trial in China for patients with non-squamous NSCLC, will assess the impact of tislelizumab given in combination with chemotherapy, as a potential way to improve outcomes in Chinese patients with advanced lung cancer, for whom prognoses are typically quite poor,” explained Lai Wang, Ph.D., Head of China Development at BeiGene.

Trial design
The Phase III, open-label, multi-center trial is expected to enroll approximately 340 chemotherapy naïve patients with Stage IIIB or IV squamous NSCLC in mainland China who will be randomized to receive carboplatin and paclitaxel, carboplatin, paclitaxel and tislelizumab, or carboplatin, nab-paclitaxel and tislelizumab.

The trial is designed to compare progression-free survival (PFS) as assessed by the Independent Review Committee (IRC) per RECIST v1.1. Key secondary endpoints include overall survival, overall response rate, duration of response, PFS by investigator assessment, and safety and tolerability.

References
[1] Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J.
Cancer statistics in China, 2015.CA Cancer J Clin. 2016 Mar-Apr;66(2):115-32. doi: 10.3322/caac.21338. Epub 2016 Jan 25.
[2] American Cancer Society. Non-Small Cell Lung Cancer. https://www.cancer.org/cancer/nonsmall-cell-lung-cancer.html. Last Accessed August 8, 2018.


Last Editorial Review: August 8, 2018

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