Cadonilimab represents a new class of cancer treatment within the field of immunotherapy. It is a novel bispecific antibody, designed to target specific pathways involved in the body’s immune response to cancer. It signifies an evolving approach to harnessing the immune system to fight malignant cells.
Mechanism of Action
The immune system naturally possesses built-in “brakes” known as immune checkpoints, such as Programmed Death-1 (PD-1) and Cytotoxic T-Lymphocyte-Associated protein 4 (CTLA-4). Cancer cells can exploit these checkpoints to evade detection and destruction by the body’s own immune cells, particularly T cells. By engaging these checkpoints, tumors essentially tell the immune system to stand down, allowing cancer to grow unchecked.
Cadonilimab is a unique bispecific antibody, engineered to bind to two distinct targets simultaneously. Specifically, it targets both PD-1 and CTLA-4, acting like a single key that can unlock two different security systems on cancer cells. This dual blockade is designed to release the “brakes” on the immune system, thereby promoting the activation of tumor-specific T cells and inhibiting tumor growth.
The design of cadonilimab is also notable for its Fc-null structure, a modified fragment crystallizable region. This modification helps to minimize unwanted immune reactions like antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC). This specialized structure may also allow the drug to stay in tumor tissues longer and bind more effectively where PD-1 and CTLA-4 are highly expressed. By simultaneously blocking both pathways, cadonilimab significantly increases the release of immune-activating molecules such as interleukin-2 (IL-2) and interferon-γ (IFN-γ), leading to a robust anti-tumor response.
Approved Uses and Clinical Trials
Cadonilimab has received regulatory approval in China for specific cancer indications. It is approved for treating recurrent or metastatic cervical cancer that has progressed following platinum-based chemotherapy, and for the first-line treatment of advanced gastric cancer.
More recently, cadonilimab gained approval in China for the first-line treatment of persistent, recurrent, or metastatic cervical cancer when used in combination with platinum-based chemotherapy, with or without bevacizumab. This approval makes it the first bispecific antibody targeting both PD-1 and CTLA-4 to be approved globally. Beyond its approved uses, cadonilimab is being investigated in over 23 clinical trials across more than 16 different cancer types.
These ongoing investigations include studies in gastric, liver, and lung cancers. In the Phase III COMPASSION-16 study for first-line cervical cancer, the cadonilimab combination regimen demonstrated significant improvements in both progression-free survival and overall survival. For advanced cervical cancer in a first-line setting, one study reported an objective response rate of 81.3%. In patients with HER2-negative gastric cancer, the COMPASSION-04 trial showed a median progression-free survival of approximately 8.18 months and a median overall survival of about 17.48 months when cadonilimab was combined with chemotherapy.
Administration of Cadonilimab
Cadonilimab is administered through an intravenous (IV) infusion. It typically takes place in a hospital or a specialized clinic setting, ensuring patients receive careful medical supervision during treatment. The drug is delivered directly into the bloodstream via an IV line.
A single infusion session typically lasts about 60 minutes. The frequency of these treatments can vary, but a common schedule involves infusions every two weeks or every three weeks. During and after the infusion, healthcare professionals monitor patients for reactions or side effects.
Side Effects and Safety Profile
As cadonilimab works by activating the immune system, its side effects are related to immune stimulation. These immune-related adverse events can affect various organ systems. Patients are closely monitored by their healthcare team to manage these potential risks effectively.
Common side effects include infusion-related reactions (approximately 18.5%), such as fever, chills, rash, or a drop in blood pressure, which are mostly mild to moderate. Other frequent side effects include fatigue (about 15.1%), skin rash (around 17.6%), itching (pruritus, 16.8%), or gastrointestinal issues like nausea (approximately 28.6%).
More serious immune-related side effects can involve organs such as inflammation of the liver (hepatitis), lung tissue (pneumonitis), or the colon (colitis). Endocrine glands, including the thyroid, can also be affected, leading to thyroid dysfunction. While serious events can occur, the unique Fc-null design of cadonilimab may contribute to a reduced incidence of severe toxicities compared to some other combination immunotherapies. In clinical trials, grade 3 or higher adverse events have been observed, and some patients discontinued treatment due to adverse events, though no treatment-related deaths were reported.