Nofazinlimab is an investigational immunotherapy drug being developed for cancer treatment. It is a type of monoclonal antibody, specifically a humanized immunoglobulin G4 (IgG4), that is engineered to recognize and bind to a specific protein on immune cells. The drug is being studied for its potential use in treating various solid tumors.
Mechanism of Action
Nofazinlimab functions by targeting a protein on the surface of T-cells called programmed cell death protein-1 (PD-1). T-cells are a type of immune cell that can attack and destroy cancer cells. Some cancer cells have a corresponding protein on their surface called programmed death-ligand 1 (PD-L1). When PD-1 on a T-cell binds to PD-L1 on a cancer cell, it acts as an “off switch,” preventing the T-cell from attacking the cancer.
This drug works by blocking the interaction between PD-1 and PD-L1. By attaching to the PD-1 receptor on T-cells, nofazinlimab prevents cancer cells from deactivating them. This action effectively releases a natural brake on the immune system, allowing the T-cells to recognize and attack cancerous tissues. This mechanism is a common strategy in a field of cancer treatment known as checkpoint inhibition.
The design of nofazinlimab as a humanized IgG4 monoclonal antibody is a specific choice to facilitate this function. This structure is intended to effectively block the PD-1 pathway while minimizing other immune system reactions that could lead to side effects.
Clinical Applications and Target Cancers
The main focus of nofazinlimab’s clinical development has been on its use for unresectable hepatocellular carcinoma (uHCC). Hepatocellular carcinoma is the most common type of primary liver cancer, and “unresectable” means the tumor cannot be completely removed with surgery. This often applies to patients with advanced or widespread disease where systemic treatments that circulate through the body are required.
In clinical studies, nofazinlimab is primarily evaluated as part of a combination therapy with lenvatinib. Lenvatinib is a type of cancer drug known as a tyrosine kinase inhibitor. Its function is to block proteins that signal cancer cells to grow and divide. It also helps stop the formation of new blood vessels that tumors need to expand.
The strategy is to attack the cancer from two different angles, combining nofazinlimab’s immune-boosting effect with lenvatinib’s direct inhibition of tumor growth and blood supply. The U.S. Food and Drug Administration (FDA) granted nofazinlimab Orphan Drug Designation for the treatment of HCC. This status is given to support the development of drugs for rare diseases.
Clinical Trial Findings
Clinical trial data for the nofazinlimab and lenvatinib combination has provided insights into its efficacy for uHCC. In a Phase 1b study with Chinese patients, the combination showed an objective response rate (ORR) of 45.0%. The ORR measures the proportion of patients whose tumors shrink by a specified amount. This response was noted as being durable, lasting from 4.2 to over 18.7 months at the time of data analysis.
Further metrics showed a median progression-free survival (PFS) of 10.4 months. PFS is the length of time a patient lives with the disease without it getting worse. These early-phase findings informed the design of a larger, international Phase 3 study to confirm the results, which has completed patient enrollment. A final analysis of overall survival is expected in 2025.
Regarding safety, the combination of nofazinlimab and lenvatinib was found to be well-tolerated with a manageable safety profile. In a separate Phase 1 study of nofazinlimab as a monotherapy for various advanced solid tumors, the treatment was also well-tolerated. No dose-limiting toxicities were observed, and a recommended dose for further studies was established.
Regulatory and Developmental Status
Nofazinlimab is an investigational drug and has not received approval from the FDA or other major international regulatory bodies for commercial use. It cannot be prescribed to patients outside of clinical trials. The drug’s development is led by CStone Pharmaceuticals.
The company has pursued partnerships to advance the drug’s development. After initial collaborations, the rights to nofazinlimab outside of Greater China were returned to CStone, which is now seeking new partnership opportunities.
The path to potential approval involves submitting extensive data from clinical trials to agencies like the FDA in a Biologics License Application (BLA). The company expects the final overall survival analysis from its Phase 3 trial in the first half of 2025. This data will be a determining factor in future regulatory submissions.