LEPU BIO-B MRG004A (TF ADC) has been approved by CDE to initiate Phase III clinical trials for pancreatic cancer

According to the Zhitong Finance APP, on August 1st, the Center for Drug Evaluation (CDE) of the National Medical Products Administration announced that the antibody-drug conjugate (ADC) MRG004A, independently developed by LEPU BIO-B (02157) targeting tissue factor (TF), has officially launched a Phase III clinical trial for pancreatic cancer. This significant progress marks a key step closer to the market for this innovative drug and brings new hope for the treatment of pancreatic cancer, known as the "king of cancers." Public information shows that MRG004A is an innovative antibody-drug conjugate (ADC) developed by LEPU BIO-B, specifically conjugated to target tissue factor (TF). It utilizes internationally leading Glyco ConnectTM site-specific conjugation and Hydra SpaceTM polar spacer technology to link the TF-targeting monoclonal antibody with the highly effective microtubule inhibitor MMAE. TF is a transmembrane glycoprotein that plays a key role in the coagulation cascade and is highly expressed in various tumors, such as pancreatic cancer, cervical cancer, triple-negative breast cancer, and ovarian cancer. Multiple signaling pathways in tumor cells induce TF expression and are involved in tumor cell proliferation, survival, migration, and tumor angiogenesis. Therefore, TF has attracted attention as a target for tumor therapy. The mechanism of action of MRG004A is highly precise: it first recognizes and binds to the TF antigen, which is overexpressed on the surface of cancer cells, through the antibody portion. Subsequently, the antigen-antibody complex enters the cancer cell via receptor-mediated endocytosis, where it is released from the lysosome after being degraded by proteases, releasing the cytotoxin MMAE, leading to cancer cell death. This "biological missile" targeted delivery mechanism maximizes the drug concentration at the tumor site while minimizing toxicity to normal tissues. Compared to traditional chemotherapy drugs, MRG004A has multiple advantages: strong targeting, relatively controllable side effects; it may still be effective in advanced patients who have failed standard treatments; and it has potential synergistic effects when used in combination with immune checkpoint inhibitors. The Phase I/II clinical study data for MRG004A were presented in a verbal report at the 2024 American Society of Clinical Oncology (ASCO) annual meeting. MRG004A demonstrated significant anti-tumor activity in pancreatic cancer patients. In the 2.0 mg/kg dosage group, among 12 evaluable pancreatic cancer patients (with a median of 3 prior treatment lines), there were 4 cases of partial response (PR) and 6 cases of stable disease (SD). The objective response rate (ORR) was 33.3% (4/12), and the disease control rate (DCR) was 83.3% (10/12). Among them, 5 pancreatic cancer patients with a TF expression rate ≥50% and an intensity of 3+ achieved 4 cases of PR and 1 case of SD after receiving treatment at a dosage of 2 mg/kg Based on positive clinical data, MRG004A has successively obtained multiple regulatory qualifications. In December 2023, MRG004A received orphan drug designation from the FDA for the treatment of pancreatic cancer. In March 2024, LEPU BIO announced that MRG004A has been granted fast track designation by the FDA for the treatment of pancreatic cancer. It is well known that the mortality rate of pancreatic cancer is very high, with a 5-year overall survival rate of only about 10% for advanced pancreatic cancer. The median survival time for first-line treatment of advanced pancreatic cancer is less than one year, and the median survival time for second-line treatment is about 6 months. Currently, there is no standard treatment for third-line pancreatic cancer, and historical data reports that the overall survival time for third-line and beyond pancreatic cancer is only about three months. In recent years, while new drugs and technologies have flourished in solid tumors, pancreatic cancer has stubbornly maintained its title as the "king of cancers." Despite some progress in drug treatment, the improvement in prognosis for pancreatic cancer lags far behind that of other solid tumors. This time, LEPU BIO's MRG004A has initiated a Phase III clinical trial for pancreatic cancer, which is expected to bring new treatment hope for patients with advanced pancreatic cancer. If the Phase III clinical trial is successful, MRG004A will inject new vitality into the field of pancreatic cancer treatment and change the existing treatment landscape