#China #Chengdu #Kelun-Biotech #sacituzumab-tirumotecan #TROP2-ADC

Sichuan Kelun-Biotech's Fourth NDA Acceptance for sacituzumab tirumotecan

Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. has recently announced an important advancement in the oncology sector with the acceptance by the Center for Drug Evaluation (CDE) of China for a new indication application of its leading monoclonal antibody-drug conjugate (ADC) therapy, sacituzumab tirumotecan (sac-TMT). This acceptance marks the company's fourth NDA application for sac-TMT, which aims to treat adult patients suffering from unresectable locally advanced, metastatic hormone-receptor positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer who have already undergone prior endocrine therapy and other systemic treatments.

This landmark decision was influenced by promising results from the registrational phase 3 clinical study known as OptiTROP-Breast02. This randomized, open-label investigation tested the efficacy and safety of sac-TMT administered every two weeks (5 mg/kg) against a physician's choice of chemotherapy in treating patients with advanced breast cancer classified as HR+/HER2-. The primary objective, progression-free survival (PFS), was met based on a pre-specified interim analysis, showing a statistically significant and clinically relevant improvement when compared to the standard chemotherapy options.

Moreover, the results indicated a positive trend in overall survival (OS) rates among patients treated with sac-TMT, further augmenting hopes for future application in wider oncological settings. The CDE approved the review process for this NDA via a priority pathway, a notable recognition as sac-TMT becomes the fourth indication entered into expedited evaluation from the CDE following prior approvals.

Dr. Michael Ge, CEO of Kelun-Biotech, expressed his satisfaction regarding this development, highlighting its significance as a breakthrough in breast cancer treatment methodologies. He emphasized that the approval reinforces the innovative nature of sac-TMT, aligning perfectly with the company’s commitment to center its efforts around patients’ welfare. The ongoing research aims not only to improve existing therapeutic outcomes but ultimately to address additional clinical needs that remain unmet in oncology.

Understanding HR+/HER2- Breast Cancer

Breast cancer, a leading cause of cancer-related mortality in women globally, exhibits various subtypes, with HR+/HER2- accounting for approximately 70% of cases. In 2022, there were about 2.3 million diagnoses and about 666,000 deaths attributed to breast cancer. Patients with this subtype exhibit hormone sensitivity, making endocrine therapy the first-line treatment, often combined with CDK4/6 inhibitors. Unfortunately, once the disease progresses to an advanced stage, existing treatments often fall short, creating an urgent need for innovative therapies that can provide meaningful survival benefits.

Currently, there is a significant unmet clinical need for patients who exhibit resistance to first-line hormonal therapies, particularly those who have advanced or metastatic HR+/HER2- breast cancer. Sac-TMT seeks to fill this gap.

Innovative Approach of sac-TMT

Sac-TMT is a novel human TROP2 ADC that exemplifies a significant advancement in treatment strategy for solid tumors. Featuring a specialized linker that connects a topoisomerase I inhibitor (derived from belotecan) to a humanized anti-TROP2 monoclonal antibody, sac-TMT effectively targets tumor cells through a dual action mechanism. It binds to TROP2 on tumor cells, leading to internalization and, ultimately, the release of KL610023, the active metabolite, which damages DNA and induces apoptosis in cancer cells. The design of sac-TMT notably includes a potential for a bystander effect where adjacent tumor cells can also be affected by the released cytotoxic agent.

In 2022, Kelun-Biotech granted exclusive rights to MSD (Merck & Co., Inc.) for the development and commercialization of sac-TMT outside Greater China. This partnership has already initiated various Phase 3 global clinical studies, expanding the horizon for sac-TMT as a leading oncological therapy.

Today, Kelun-Biotech proudly acknowledges that sac-TMT is the first ADC developed domestically in China to gain comprehensive approval for marketing with global intellectual property rights. This pivotal change signals an era where innovative treatment options become accessible to patients globally, aiming to address life-threatening conditions that require immediate and effective intervention.

In conclusion, the acceptance of the fourth NDA for sac-TMT is not only a commendable milestone for Kelun-Biotech but also a beacon of hope for breast cancer patients worldwide seeking new therapeutic options. As the company anticipates longitudinal studies to reveal further survival benefits, the future of cancer treatment looks promising.