Loqtorzi

Nasopharyngeal Carcinoma

Loqtorzi is used to treat nasopharyngeal carcinoma (NPC), which is a cancer that starts in the upper part of the throat behind the nose. It is approved for use in adults in the following situations:

• First-line treatment: It is used in combination with the chemotherapy medications cisplatin and gemcitabine for patients whose cancer has spread to other parts of the body (metastatic) or has returned in a nearby area (locally advanced).
• Subsequent treatment: It is used alone (as monotherapy) for patients whose cancer has returned, cannot be removed by surgery, or has spread, and has continued to grow despite previous treatment with platinum-based chemotherapy.

Loqtorzi is a type of immunotherapy known as a PD-1 inhibitor. It works by helping the immune system recognize and attack cancer cells. It is administered as an intravenous (IV) infusion by a healthcare professional in a medical setting.

Mechanism of Action

Loqtorzi belongs to a class of drugs known as monoclonal antibodies, specifically programmed death receptor-1 (PD-1) blockers. It works by targeting a specific pathway used by cancer cells to avoid being detected by the immune system.

The immune system uses T-cells to find and destroy abnormal cells. However, some cancer cells produce proteins that bind to the PD-1 receptor on T-cells, effectively turning off the immune response. Loqtorzi binds to these PD-1 receptors, preventing cancer cells from deactivating the T-cells.

By blocking this interaction, the medication allows the immune system to:

• Recognize cancer cells as a threat.
• Activate T-cells to attack the tumor.
• Slow or stop the growth of the cancer.

Because this drug works by stimulating the immune system, it is considered a type of immunotherapy rather than traditional chemotherapy.

Common Side Effects

The most common side effects of Loqtorzi, particularly when used in combination with chemotherapy, include:

• Fatigue and weakness
• Nausea and vomiting
• Diarrhea or constipation
• Decreased appetite
• Muscle, bone, or joint pain
• Rash or itchy skin
• Cough
• Hair loss
• Low thyroid hormone levels (hypothyroidism)

Serious Side Effects

Loqtorzi can cause the immune system to attack normal organs and tissues, leading to serious or life-threatening conditions. These reactions can happen at any time during or after treatment.

Immune-Mediated Reactions

• Lung problems: New or worsening cough, chest pain, or shortness of breath (pneumonitis).
• Intestinal problems: Severe diarrhea, blood in stools, or severe stomach pain (colitis).
• Liver problems: Yellowing of the skin or eyes, dark urine, or pain on the right side of the stomach (hepatitis).
• Hormone gland problems: These may affect the thyroid, pituitary, or adrenal glands, or the pancreas (Type 1 diabetes).
• Kidney problems: Changes in urine output or swelling in the ankles (nephritis).
• Skin reactions: Severe rashes, itching, blistering, or peeling skin.

Infusion Reactions

Some people may have a reaction to the infusion itself. Tell your healthcare provider immediately if you experience chills, shaking, dizziness, fever, flushing, or difficulty breathing during the injection.

Immune-Mediated Adverse Reactions

Loqtorzi is an immunotherapy that works by helping the immune system attack cancer cells. However, it can also cause the immune system to attack healthy organs and tissues in any part of the body. These reactions can be severe or fatal and may occur at any time during or after treatment. Common areas affected include:

• Lungs: Inflammation of the lungs (pneumonitis).
• Intestines: Inflammation of the colon (colitis) that can lead to tears or holes in the intestines.
• Liver: Inflammation of the liver (hepatitis).
• Hormone glands: Issues with the thyroid, pituitary, or adrenal glands, and type 1 diabetes.
• Kidneys: Inflammation of the kidneys (nephritis) or kidney failure.
• Skin: Severe rashes or blistering.

Infusion-Related Reactions

Severe or life-threatening infusion reactions can occur. Medical staff monitor for signs such as chills, shaking, itching, flushing, shortness of breath, dizziness, or fever during the administration of the drug.

Stem Cell Transplant Risks

There are increased risks of serious complications, including graft-versus-host disease, in people who have received or will receive a stem cell transplant using donor cells (allogeneic hematopoietic stem cell transplant).

Pregnancy and Reproduction

Loqtorzi can cause harm to a fetus. Verification of pregnancy status is typically performed before starting treatment. Effective birth control is recommended for females of reproductive potential during treatment and for four months after the final dose. Breastfeeding is generally not recommended during treatment and for a period following the final dose.

Monitoring

Regular blood tests are used to monitor organ function throughout treatment. This includes checking liver function, thyroid function, kidney function, and blood sugar levels to detect early signs of immune-mediated reactions.

Pregnancy

Loqtorzi (toripalimab-tpzi) can cause harm to an unborn baby if used during pregnancy. Based on how the drug works in the body, it may interfere with the immune system's ability to maintain a pregnancy. Animal studies have indicated that blocking the PD-1 pathway, which this medication does, can increase the risk of pregnancy loss or stillbirth.

Patients who can become pregnant should have a pregnancy test before starting treatment. It is important to use effective birth control (contraception) during treatment and for at least 4 months after the last dose of Loqtorzi. If a patient becomes pregnant while receiving this medication, they should notify their healthcare provider immediately.

Breastfeeding

It is not known whether toripalimab-tpzi passes into human breast milk or how it might affect a nursing infant. Because of the potential for serious adverse reactions in a breastfed child, healthcare providers generally advise against breastfeeding during treatment and for 4 months after the final dose.

Dosage Forms

Loqtorzi is supplied as a liquid solution for intravenous administration. It comes in the following format:

• Intravenous Injection: A clear to slightly opalescent, colorless to slightly yellow solution provided in a single-dose vial.

This medication is a sterile, preservative-free solution that must be diluted by a healthcare provider before use.

FDA Approval Status

The U.S. Food and Drug Administration (FDA) approved Loqtorzi (toripalimab-tpzi) in October 2023. It was the first immunotherapy approved by the FDA specifically for the treatment of nasopharyngeal carcinoma (NPC).

Approved Indications

Loqtorzi is indicated for use in adult patients in two specific clinical scenarios:

• First-line treatment: In combination with the chemotherapy drugs cisplatin and gemcitabine for the treatment of metastatic or recurrent locally advanced NPC.
• Subsequent treatment: As a single agent for the treatment of recurrent, unresectable, or metastatic NPC that has progressed on or after platinum-containing chemotherapy.

Regulatory Safety Information

As of its approval, Loqtorzi does not carry a boxed warning, and there is no Risk Evaluation and Mitigation Strategy (REMS) program required. However, the FDA-approved labeling includes significant warnings regarding immune-mediated adverse reactions. These reactions occur when the immune system attacks healthy organs or tissues, potentially affecting the lungs, liver, colon, endocrine glands, and kidneys. Healthcare providers are required to monitor patients for these complications and may need to withhold or discontinue treatment if they occur.

Insurance Coverage

Loqtorzi is an intravenous medication administered by healthcare professionals, meaning it is usually covered under a medical insurance policy rather than a standard prescription drug plan. Coverage levels can vary significantly between private insurance, Medicare, and Medicaid. Most insurers require prior authorization to confirm the medication is medically necessary before they will agree to pay for it.

Administration Costs

The total price of treatment often includes more than just the cost of the drug itself. Patients may also be billed for:

• Facility fees for the hospital or clinic where the infusion is given.
• Nursing or professional fees for the administration of the drug.
• Supplies used during the infusion process.

Financial Assistance Programs

Because Loqtorzi is a specialty biologic medication, the manufacturer may offer patient assistance programs. These programs can include co-pay assistance for patients with commercial insurance or programs that provide the medication at no cost to eligible patients who are uninsured or have limited income. Patients should consult with their oncology team or a financial counselor at their treatment center to identify available support options.