Boehringer Ingelheim announced that its innovative drug MDM2-p53 antagonist BI 907828 was used for the first-line treatment of dedifferentiated liposarcoma (DDLPS) Phase II/III clinical trial Brightline-1 (registration number: CTR20222584), in West China Hospital of Sichuan University The first DDLPS patient was successfully enrolled. Brightline-1 is a randomized, open-label, global multi-center phase II/III clinical trial, aiming to compare the efficacy and safety of BI 907828 and doxorubicin as first-line treatment in patients with advanced DDLPS. The study China The main investigator (leading PI) is Professor Zhang Xing from Sun Yat-sen University Cancer Center.
‘The Forgotten Cancer’ – Sarcomas Facing Difficulties
Sarcomas are rare malignant tumors that occur in connective tissues such as bone, cartilage, muscle, nerves, blood vessels, and fatty and fibrous tissues, accounting for approximately 1% of all cancers worldwide. 87.3% of sarcomas occur in soft tissues, such as muscle, nerve, blood vessel, fat and fibrous tissue, these are called soft tissue sarcoma (STS), and there are many subtypes, liposarcoma (LPS) is the most common One of the subtypes; the other 12.7% of sarcomas are osteosarcomas, which mostly originate from bone or cartilage. According to the statistics of the SEER database of the National Cancer Institute (NCI), the total incidence of sarcoma is less than 5/100,000 per year.
Due to the rarity of sarcoma and insufficient awareness of the disease among clinicians, accurate diagnosis and subsequent standardized treatment are delayed. When most patients with sarcoma are diagnosed, the disease is already at an advanced stage for which treatment options are scarce—chemotherapy has been the mainstay of treatment for nearly 50 years. Dedifferentiated liposarcoma (DDLPS) is a highly aggressive subtype of LPS, with a recurrence rate as high as 40%-75% and a metastasis rate of 10%-15%, which is significantly higher than other LPS subtypes and has a poorer clinical outcome. At the same time, the effect of DDLPS chemotherapy is poor, and these patients urgently need more effective and less toxic treatment options.
MDM2-p53 antagonist BI 907828 is an orally administered small molecule compound that inhibits the interaction between MDM2 and p53 proteins. P53 is a tumor suppressor that drives tumor cell death, and MDM2 is a major negative regulator of p53, which can bind to p53 and promote its clearance, and MDM2 gene amplification is the most common gene alteration in DDLPS, in 90% of It exists in DDLPS cases, laying the foundation for the wide application of BI 907828 in DDLPS.
BI 907828 has the potential to transform the treatment of cancer patients driven by MDM2-p53 axonal mutations
BI 907828 has demonstrated preliminary potential in the treatment of DDLPS. At the 2022 European Society of Medical Oncology (ESMO) Congress, the dose expansion phase Ib study data of BI 907828 in patients with TP53 wild-type, MDM2-amplified solid tumors showed that BI 907828 has a positive effect on The disease control rate (DCR) of DDLPS was 93%, of which 2 patients achieved partial remission (PR), and the progression-free survival (PFS) of 5 patients with DDLPS was >10.5 months, and the adverse reactions were safe and controllable.
Professor Zhang Xing from Sun Yat-sen University Cancer Center said: “The official launch of BI 907828 Phase II/III clinical trials is of great significance, bringing new hope to Chinese patients with DDLPS, enabling patients with these rare tumor types to be contacted in the first place To the first/breakthrough treatment methods and drugs. In addition, with the help of Boehringer Ingelheim’s clinical research cooperation project, Chinese clinical researchers can carry out research and development plans and clinical trials in a “zero time difference” with the world. The significance of the promotion is also self-evident-while improving the clinical research capabilities of Chinese researchers, it also actively promotes the progress of China’s trials, so that more Chinese DDLPS patients can use innovative drugs as soon as possible.”
Professor Jiang Yu from West China Hospital of Sichuan University said: “DDLPS patients have long lacked effective treatment methods, and the emergence of BI 907828 has undoubtedly opened a ‘new door’ for these patients. BI 907828 has shown in phase Ib trials It has shown encouraging therapeutic potential, and the successful enrollment of the first patient in our hospital indicates that Chinese patients can benefit from innovative drugs earlier, and the needs of Chinese patients can be reflected in the research and development plan earlier, The Chinese data can be applied to clinical practice in the first time, and I am looking forward to the clinical benefits that BI 907828 can bring to more patients.”
Dr. Zhang Wei, head of Boehringer Ingelheim’s China Medicine and R&D, said: “We are very pleased to see that the phase II/III clinical trial of BI 907828 has made progress, and the first patient has been successfully enrolled in China. The early efficacy data of BI 907828 has already It has shown certain potential. Based on evidence-based medical evidence and clinical needs, the U.S. Food and Drug Administration (FDA) has granted BI 907828 orphan drug designation for the treatment of soft tissue sarcoma, including DDLPS. Thanks to ‘China Key’ (China The in-depth development of the ‘Key)’ project has enabled Chinese patients, Chinese researchers, and Chinese treatment centers to participate in global early-stage research. The Brightline-1 study is just another extension of the ‘China Key’ project. Based on the ‘Winning in Oncology ”Global strategy, Boehringer Ingelheim is currently actively deploying tumor drug pipelines, continuously optimizing existing tumor treatment methods and striving to develop innovative therapies. patients worldwide.”
