2021 AACR: BeiGene Reveals Global Phase III Clinical Data of Baizean® for Second/Third-line Treatment of Patients with Advanced Non-Small Cell Lung Cancer

On April 13, 2021, Beijing time, BeiGene's self-developed anti-PD-1 antibody-drug Bezean® (tislelizumab) compared with docetaxel for the second disease progression after platinum-based chemotherapy /Detailed data of the global phase III clinical trial (RATIONALE 303 study) in patients with third-line locally advanced or metastatic non-small cell lung cancer was disclosed at the 112th American Cancer Society Annual Meeting (AACR).

Previously, BeiGene announced that the study had reached the primary endpoint of overall survival (OS) in the interim analysis, and in January this year, it submitted a new report to the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA). Application for listing of indications. The RATIONALE 303 study is a key global clinical trial with positive results for Bezeran® (tislelizumab), which once again confirms BeiGene's global clinical development capabilities. So far, Bezian® (Tilelizumab) has also become the world's only PD-1 monoclonal antibody that benefits the entire population of advanced non-small cell lung cancer first and second-line, and the only PD-1 monoclonal antibody independently developed in China Drugs that have achieved a positive result for the primary endpoint of OS in phase III clinical study of lung cancer.

Lung cancer is currently the number one malignant tumor in my country in terms of morbidity and mortality. Non-small cell lung cancer is the most common type of lung cancer, accounting for about 80%-85% of the total number of lung cancers. About 70% of patients are already at an advanced stage at the time of diagnosis and cannot be operated on and require medical treatment.

Immunotherapy is a new direction in the treatment of lung cancer in recent years. Because of its relatively smaller side effects and the opportunity for patients to obtain long-term benefits, more and more doctors and patients have begun to pay attention to immunotherapy. With the successive approval of immunotherapy drugs in China, patients with advanced non-small-cell lung cancer with negative driver genes have new first-line treatment options besides chemotherapy. However, due to objective reasons such as the availability of drugs and the screening of drug users, there are still many patients with advanced non-small-cell lung cancer in China who cannot use immunotherapy in the first-line treatment. For these patients, their second-line treatment options are also very scarce. Although nivolumab has been approved for the treatment of second-line non-small cell lung cancer in China, it is restricted by factors such as drug availability. Representative chemotherapy is still a widely used treatment option for second-line non-small cell lung cancer. At present, the medication status of patients with second-line non-small cell lung cancer in China has not been effectively improved, and there is an urgent need for more and better drugs to improve the treatment of patients with second-line non-small cell lung cancer.

The RATIONALE 303 study, which released the data this time, is a randomized, open, multi-center, global phase III clinical trial conducted by BeiGene, which aims to evaluate Beizian® (tislelizumab) versus docetaxel The efficacy and safety of Cyx for the treatment of second/third-line locally advanced or metastatic non-small cell lung cancer patients who have undergone disease progression after receiving platinum-based chemotherapy. The study enrolled 805 patients in 10 countries around the world and randomly enrolled them at a ratio of 2:1 to the Bezian® (tislelizumab) monotherapy group or the docetaxel control group.

From the data released this time, compared with traditional chemotherapy, Bezian® (tislelizumab) has shown more significant clinical benefits, specifically in:

1. Significantly prolong the overall survival of patients: Compared with chemotherapy, the use of Bezian® (tislelizumab) can reduce the risk of death of patients by 36%, and prolong the median overall survival by nearly half a year to nearly one and a half years ( 17.2m vs. 11.9m); the 2-year OS rate was 1.6 times that of the chemotherapy group (39.4% vs. 25.0%).

2. Regardless of PD-L1 expression, the entire patient population benefits: Compared with other immunotherapy programs that need to detect PD-L1 expression to determine the benefit population, Bezian® (Tilelizumab) can make the second/third line The whole population of non-small cell lung cancer patients benefited. For patients with PD-L1≥1%, Bezian® (tislelizumab) can reduce the risk of death by 42%; for patients with PD-L1<1%, it can also reduce the risk of death by 26%.

3. Survival benefits can be shown in the early stage of treatment: In many previous clinical studies of immunotherapy, patients using immunotherapy have a slow onset of effect, and the initial effect is not obvious, which leads to the crossing of the survival curve of the study; and Baizian ® (Tilelizhu The data of monoclonal antibody) shows that it can take effect quickly. For patients with second/third-line non-small cell lung cancer, even if they receive Bezan® (tislelizumab) monotherapy, the survival curve can be separated at an early stage, and the survival benefit of patients in the early stage of treatment can exceed that of chemotherapy.

4. The objective remission rate is three times higher than that of chemotherapy: In clinical trials, more patients who used Bezian® (Tilelizumab) achieved tumor remission, and the remission rate was more than three times that of the chemotherapy group (21.9%). vs. 7.0%), the median duration of remission was more than twice that of the chemotherapy group (13.5m vs. 6.2m), and the patient benefit was longer.

5. The safety is significantly better than chemotherapy: the incidence of adverse reactions in patients using Bezian® (tislelizumab) is generally lower than that of the chemotherapy group, although the treatment cycle of patients is more than twice (9.4 Cycle vs. 4.5 cycles), the incidence of immune-related adverse reactions is still very low, and the incidence of treatment-related adverse reactions above grade 3 is only 14%, which is significantly lower than the 66% in the chemotherapy group.