The additional indication for first-line treatment of gastric and gastroesophageal junction cancers is supported by the results from BeiGene’s RATIONALE-305 trial, a global, randomized, double-blind, placebo-controlled Phase 3 study.
The trial evaluated the efficacy and safety of TEVIMBRA in combination with chemotherapy as a first-line treatment for adult patients with advanced, unresectable, or metastatic G/GEJ cancer. The study met its primary endpoint, showing a statistically significant and clinically meaningful overall survival (OS) benefit. Patients treated with TEVIMBRA combined with chemotherapy had a median OS of 15.0 months, compared to 12.9 months for those treated with placebo plus chemotherapy (n=997; HR: 0.80 [95% CI: 0.70, 0.92]; P=0.0011), reflecting a 20% reduction in the risk of death.
About Tislelizumab
Tislelizumab, marketed under the brand name Tevimbra, is an anti-cancer medication developed by BeiGene. It is a humanized monoclonal antibody that targets the programmed death receptor-1 (PD-1), a checkpoint protein found on immune cells. By blocking PD-1, tislelizumab enhances the immune system’s ability to identify and attack cancer cells. It is classified as an immune checkpoint inhibitor, part of the growing class of immunotherapies that harness the body’s immune system to combat cancer.
Medical Uses: Tislelizumab is approved for the treatment of various cancers. In China, it is used to treat classical Hodgkin lymphoma in patients who have failed at least two prior therapies and to treat locally advanced or metastatic urothelial carcinoma with high PD-L1 expression in patients whose disease has progressed after platinum-based chemotherapy. In the European Union, tislelizumab is indicated for adults with unresectable, locally advanced, or metastatic esophageal squamous cell carcinoma after prior chemotherapy and for certain types of advanced gastric or gastroesophageal junction adenocarcinoma in combination with chemotherapy. In the United States, it is indicated for the treatment of unresectable or metastatic esophageal squamous cell carcinoma after prior chemotherapy, as well as for HER2-negative gastric or gastroesophageal junction adenocarcinoma in combination with chemotherapy, provided the tumors express PD-L1.
Adverse Effects: Common side effects of tislelizumab include anemia, leukopenia (low white blood cell count), thrombocytopenia (low platelet count), nausea, fatigue, and musculoskeletal pain. More serious adverse effects can include liver damage (hepatotoxicity), respiratory infections or failure, and autoimmune reactions due to the immune system attacking normal tissues. These effects are more common when tislelizumab is combined with chemotherapy.
Pharmacokinetics: Clinical studies have shown that tislelizumab has a relatively long half-life compared to other PD-1 inhibitors like pembrolizumab and nivolumab. A 2016 Phase I trial suggested its half-life to be between 11 and 17 days. More recent analyses have shown an even longer half-life, approximately 238 minutes, which is 30 to 80 times higher than that of other similar drugs.
History: Phase I clinical trials for tislelizumab began in 2015, with results indicating its potential effectiveness. Subsequent trials have demonstrated its efficacy in treating various cancers, including hepatocellular carcinoma (liver cancer). In 2024, the drug’s approval in the U.S. and Europe was expanded to include first-line treatments for certain gastric and esophageal cancers. This drug represents a significant advancement in cancer immunotherapy, especially for cancers that have limited treatment options.
Beyond this recent approval, TEVIMBRA is also indicated as a monotherapy for unresectable or metastatic ESCC after prior chemotherapy. In clinical trials, it has been shown to improve survival rates and demonstrate tolerability, particularly in patients who had not been treated with PD-(L)1 inhibitors previously.
The safety profile of TEVIMBRA in combination with chemotherapy includes common adverse events such as neutropenia, thrombocytopenia, anemia, and fatigue. Other reactions can include pneumonia, rash, and liver enzyme abnormalities. These side effects are typical of immune checkpoint inhibitors used in combination with chemotherapy, but they are manageable with appropriate monitoring and supportive care.
TEVIMBRA is also under review for additional indications in various cancers, further solidifying its potential as a promising therapy in oncology. The drug’s approval trajectory in the U.S. and other global markets reflects BeiGene’s commitment to advancing cancer treatments and improving patient outcomes in areas of high unmet medical need.
Gastric and Gastroesophageal Junction (G/GEJ) Cancer
Gastric cancer is the fifth most common cancer globally and the fifth leading cause of cancer-related deaths. In 2022, there were nearly 1 million new cases and 660,000 deaths worldwide. In the U.S., 27,000 new cases and 11,000 deaths are expected in 2024. The five-year survival rate for gastric cancer in the U.S. is 36%, highlighting the poor prognosis and the need for improved therapies.
Gastroesophageal junction (GEJ) cancer occurs where the esophagus joins the stomach, just beneath the diaphragm. It shares similarities with both esophageal and gastric cancers, but is distinct in its location and biological behavior. GEJ cancers are challenging to treat due to their complex anatomical position and aggressive nature, emphasizing the need for more effective treatment strategies.
The prognosis for patients with gastric or GEJ cancer depends on the stage at diagnosis, treatment response, and overall health. Immunotherapies, such as TEVIMBRA (tislelizumab), offer a promising approach for first-line treatment in patients with PD-L1 positive advanced or metastatic gastric and GEJ cancers. These newer treatments are vital for extending survival and improving quality of life in patients with these challenging cancers.