Toripalimab is a type of cancer therapy that works with the body’s immune system to combat the disease. It belongs to a class of drugs known as programmed death receptor-1 (PD-1) inhibitors. These treatments are not chemotherapy or radiation; instead, they represent a form of immunotherapy that enhances the immune system’s ability to detect and destroy cancerous cells.
This drug functions as a monoclonal antibody, which is a laboratory-produced protein designed to target a specific protein. In this case, the target is the PD-1 receptor found on the surface of immune cells. The goal is to restore the immune system’s function, which has been suppressed by the cancer, allowing it to mount an effective attack against the tumor.
Approved Uses and Clinical Applications
The U.S. Food and Drug Administration (FDA) has approved toripalimab, marketed as Loqtorzi, for specific applications in treating nasopharyngeal carcinoma (NPC), a cancer that affects the area behind the nose. This approval, granted in October 2023, covers its use as a first-line treatment for adults whose NPC is metastatic or has recurred locally. In this setting, it is administered in combination with two chemotherapy drugs, gemcitabine and cisplatin.
The FDA has also approved toripalimab as a standalone treatment, or monotherapy. This application is for adults with recurrent, unresectable, or metastatic NPC whose disease has progressed despite previous treatment with platinum-based chemotherapy. The approval for both uses is a notable development, as toripalimab is the first drug specifically approved by the FDA for treating NPC.
The basis for these approvals rests on the results of two clinical trials, JUPITER-02 and POLARIS-02. The JUPITER-02 study evaluated toripalimab plus chemotherapy against chemotherapy alone. The results showed that adding toripalimab improved progression-free survival, extending the median time to 11.7 months compared to 8.0 months for chemotherapy alone. The POLARIS-02 trial supported its use as a single agent in patients who had already undergone chemotherapy.
While its primary approval in the United States is for nasopharyngeal carcinoma, toripalimab’s application extends to other cancers in different parts of the world. In China, where the drug was developed, it has been approved for treating a wider range of malignancies. These include melanoma and urothelial carcinoma, which affects the bladder and urinary system. Clinical trials are ongoing to evaluate its effectiveness in other cancers, such as those of the lung, esophagus, and liver.
Mechanism of Action
The body’s immune system has powerful cells called T-cells that are designed to find and destroy invaders, including cancer cells. To prevent these T-cells from becoming overactive and attacking healthy tissues, the immune system uses “checkpoints” which act as brakes or off-switches. One of these checkpoint proteins is the programmed death receptor-1, or PD-1, located on the surface of T-cells.
Many cancer cells have learned to exploit this natural braking system to protect themselves from the immune system. They do this by producing a partner protein called programmed death-ligand 1 (PD-L1). When the cancer cell’s PD-L1 binds to the PD-1 receptor on a T-cell, it effectively presses the “off” switch. This interaction signals the T-cell to leave the cancer cell alone, allowing the tumor to grow and spread.
Toripalimab is designed to disrupt this specific interaction. As a PD-1 inhibitor, it functions as a blocking agent whose monoclonal antibodies bind directly to the PD-1 receptors on the T-cells. By occupying this space, toripalimab prevents the PD-L1 on cancer cells from connecting with the T-cell’s off-switch, which “releases the brakes” on the immune system.
With the PD-1 pathway blocked, the T-cells are no longer suppressed by the cancer cells. They remain active and are able to recognize the cancer cells as foreign and harmful. This restored recognition allows the immune system to mount a potent attack, leading to the destruction of tumor cells. The drug itself does not kill cancer cells directly; it empowers the patient’s own immune system to perform its intended function.
Administration and Treatment Process
Toripalimab is delivered directly into a patient’s bloodstream via an intravenous (IV) infusion. This procedure ensures that the full dose of the medication enters circulation to reach the immune cells throughout the body. The infusion is conducted in a clinical setting, such as a hospital or a specialized infusion center, under the supervision of healthcare professionals.
The treatment schedule for toripalimab can vary depending on whether it is being used alone or in combination with chemotherapy. When given with cisplatin and gemcitabine for the first-line treatment of NPC, a 240 mg dose is administered every three weeks. If used as a single agent for previously treated NPC, the recommended dosage is 3 mg per kilogram of body weight, given every two weeks.
Each infusion session lasts about 30 minutes, and patients will remain under observation afterward to monitor for any immediate reactions. This regular, cyclical treatment continues until the disease progresses or if a patient experiences unacceptable toxicity. The first-line combination therapy can last up to 24 months.
Potential Side Effects
Because toripalimab works by stimulating the immune system, many of its side effects are a direct result of this increased immune activity. These are known as immune-related adverse events, where the newly activated immune system may mistakenly attack healthy organs and tissues, causing inflammation. Patients receiving toripalimab should be aware of these potential reactions and communicate with their healthcare team.
Frequently observed side effects are often manageable, but they should always be reported to a doctor. These can include:
- Feelings of fatigue
- A skin rash or itching
- A persistent cough
- Changes in thyroid function (hypothyroidism)
- Muscle or joint pain
- A decreased appetite
Less common but more serious side effects can occur and require immediate medical attention. The heightened immune response can lead to inflammation of various organs, including:
- Pneumonitis (inflammation of the lungs)
- Colitis (inflammation of the colon)
- Hepatitis (inflammation of the liver)
- Endocrinopathies (inflammation of hormone-producing glands)
It is important for individuals undergoing therapy with toripalimab to promptly report any new or worsening symptoms to their healthcare provider. Early diagnosis and management of immune-related adverse events, often with corticosteroids to suppress the immune reaction, can prevent them from becoming severe.