Rybrevant (Amivantamab)

What Is Rybrevant and What Is It Used For?

Rybrevant (amivantamab) is a cancer medicine containing a bispecific antibody designed to recognize and attach to two specific targets on cancer cells: EGFR (epidermal growth factor receptor) and MET (mesenchymal-epithelial transition factor). It is used in adults with EGFR-mutated non-small cell lung cancer (NSCLC) that has spread to other parts of the body.

Non-small cell lung cancer (NSCLC) accounts for approximately 80-85% of all lung cancers. In a significant proportion of NSCLC patients, the cancer cells carry mutations in a gene called EGFR (epidermal growth factor receptor). These EGFR mutations drive the growth and survival of cancer cells by sending abnormal growth signals. Rybrevant was developed specifically to target these mutated cancer cells through a novel dual-targeting approach.

Unlike traditional targeted therapies that block only one protein, Rybrevant is a bispecific antibody that simultaneously targets two proteins found on cancer cell surfaces: EGFR and MET. This dual-targeting mechanism is particularly important because MET amplification is a common resistance mechanism that develops when cancers are treated with EGFR-targeted therapies alone. By blocking both pathways simultaneously, Rybrevant can help overcome this resistance.

Rybrevant works through several mechanisms. By binding to EGFR and MET, it blocks the natural signals (ligands) that would normally activate these receptors and promote cancer cell growth. Additionally, it triggers the destruction of these receptors on the cell surface through a process called receptor degradation. The antibody also recruits the body's own immune cells to attack cancer cells through a mechanism known as antibody-dependent cellular cytotoxicity (ADCC) and trogocytosis.

When is Rybrevant prescribed?

Rybrevant may be prescribed in two main clinical settings for adults with advanced EGFR-mutated NSCLC:

• First-line treatment: As the first cancer medicine you receive, given in combination with another targeted therapy called lazertinib
• After chemotherapy failure: When chemotherapy is no longer controlling your cancer, Rybrevant may be used as a subsequent line of therapy

Your oncologist will determine whether Rybrevant is appropriate for you based on the specific EGFR mutations found in your tumor, your overall health status, and your treatment history. Tumor mutation testing is required before starting treatment to confirm that your cancer carries the appropriate EGFR mutations.

What Should You Know Before Receiving Rybrevant?

Before receiving Rybrevant, inform your healthcare team about any history of lung inflammation (interstitial lung disease), current medications, pregnancy plans, and known allergies. Do not use Rybrevant if you are allergic to amivantamab or any of its ingredients. Effective contraception is required during treatment and for 3 months after the last dose.

Contraindications

You should not receive Rybrevant if you are allergic (hypersensitive) to amivantamab or any of the other ingredients in this medicine, including polysorbat 80, disodium edetate, L-methionine, sodium acetate trihydrate, and sucrose. If you are unsure whether any of these apply to you, talk to your doctor or nurse before receiving Rybrevant.

Warnings and Precautions

Talk to your doctor or nurse before receiving Rybrevant if you have a history of lung inflammation (a condition called interstitial lung disease or pneumonitis). Several important warnings apply during treatment:

• Injection-related reactions: Reactions may occur during or after the injection, particularly with the first dose. Your healthcare team will monitor you and may give you pre-medications to reduce this risk
• Lung inflammation (ILD/pneumonitis): Tell your doctor immediately if you experience sudden breathing difficulties, cough, or fever during treatment. This condition can be life-threatening and may require stopping Rybrevant permanently
• Blood clots (with lazertinib): When Rybrevant is used together with lazertinib, life-threatening blood clots in the veins (venous thromboembolism) may occur. Your doctor will prescribe additional medication to prevent blood clots and will monitor you closely
• Skin problems: Skin reactions including rash, acne, dry skin, and nail infections are very common. Use protective clothing, broad-spectrum sunscreen (UVA/UVB), and ceramide-based moisturizers regularly on your face and body (except scalp) throughout treatment. Avoid direct sun exposure during treatment and for 2 months after stopping
• Eye problems: Contact your doctor immediately if you experience vision problems or eye pain. If you wear contact lenses and develop new eye symptoms, stop wearing them and contact your doctor immediately

Pregnancy and Breastfeeding

Rybrevant may harm an unborn baby. If you are pregnant, think you may be pregnant, or are planning to become pregnant, talk to your doctor before receiving this medicine. The following guidance applies:

• Contraception: Women who could become pregnant must use effective contraception during treatment with Rybrevant and for 3 months after the last dose
• Pregnancy: If you become pregnant during treatment, tell your doctor immediately. You and your doctor will discuss whether the benefit of continuing treatment outweighs the potential risk to your unborn baby
• Breastfeeding: It is not known whether Rybrevant passes into breast milk. Discuss with your doctor whether the benefit of breastfeeding outweighs the potential risk to your child

Children and Adolescents

Rybrevant should not be given to children or young people under 18 years of age. This is because the safety and effectiveness of this medicine have not been established in this age group.

Driving and Operating Machinery

If you feel tired or dizzy, or if your eyes are irritated or your vision is affected after receiving Rybrevant, you should not drive or operate machinery until these effects have resolved.

How Does Rybrevant Interact with Other Drugs?

Tell your doctor about all medications you are currently taking or have recently taken. When Rybrevant is used in combination with lazertinib, there is an increased risk of venous thromboembolism (blood clots). Your doctor will prescribe blood clot prevention medication. No other significant drug interactions have been specifically identified for amivantamab as a monoclonal antibody.

As a monoclonal antibody, amivantamab is not metabolized by the cytochrome P450 enzyme system, which means it has fewer traditional drug-drug interactions compared to small-molecule drugs. However, there are important considerations regarding concurrent medications and combination therapy.

The most clinically significant interaction is with lazertinib, which is frequently used in combination with Rybrevant. When these two drugs are used together, patients face an increased risk of venous thromboembolism (VTE), including potentially life-threatening pulmonary embolism. To mitigate this risk, your oncologist will prescribe prophylactic anticoagulation therapy throughout treatment.

Always inform your healthcare team about all prescription medications, over-the-counter drugs, herbal supplements, and vitamins you are taking. This comprehensive medication review is essential to ensure safe treatment with Rybrevant.

What Is the Correct Dosage of Rybrevant?

Rybrevant dosage is based on body weight: 1,600 mg for patients weighing less than 80 kg, and 2,240 mg for patients weighing 80 kg or more. It is given as a subcutaneous injection once weekly for the first 4 weeks, then every 2 weeks from week 5 onward. The injection is administered by a healthcare professional in the abdomen.

Your doctor will calculate the correct dose of Rybrevant based on your body weight at the start of treatment. The medicine is given by a doctor or nurse as a subcutaneous injection (under the skin) in the abdominal area. The injection takes approximately 5 minutes.

Adults

Administration Details

Rybrevant subcutaneous injection should only be administered by trained healthcare professionals. Important administration details include:

• The injection is given in the abdominal area only — not on other parts of the body
• Injection sites must be free from redness, bruising, tenderness, hardness, tattoos, or scars
• If pain occurs during injection, the healthcare professional may pause and resume in a different area of the abdomen
• The subcutaneous formulation must not be given intravenously

Pre-medication

Before each Rybrevant injection, you will receive pre-medications to reduce the risk of injection-related reactions. These may include:

• Antihistamines to reduce allergic-type reactions
• Corticosteroids to reduce inflammation
• Antipyretics (e.g., paracetamol/acetaminophen) to prevent fever

Additional medications may be given based on any symptoms you experience during treatment.

Children

Rybrevant is not approved for use in patients under 18 years of age. Safety and efficacy have not been established in this population.

Elderly

No specific dose adjustment is required for elderly patients. Rybrevant has been studied in patients across a range of ages, including those over 65 years. However, elderly patients may be more susceptible to certain side effects and should be monitored closely throughout treatment.

Missed Dose

It is very important to attend all scheduled appointments for your Rybrevant injections. If you miss an appointment, schedule a new one as soon as possible. Your healthcare team will advise you on the best course of action to maintain your treatment schedule and ensure optimal therapeutic outcomes.

Overdose

Since Rybrevant is administered by healthcare professionals in a clinical setting, overdose is unlikely. However, if an overdose were to occur, your medical team would monitor you closely for any side effects and provide supportive care as needed. There is no specific antidote for amivantamab overdose.

What Are the Side Effects of Rybrevant?

The most common side effects of Rybrevant include injection-related reactions (chills, shortness of breath, nausea, flushing, fever), skin problems (rash, acne, dry skin, nail infections), eye problems (dry eyes, swollen eyelids), fatigue, mouth sores, nausea, vomiting, diarrhea, and decreased appetite. Serious but less common side effects include interstitial lung disease and venous thromboembolism (when used with lazertinib).

Like all medicines, Rybrevant can cause side effects, although not everybody gets them. The side effects listed below have been reported in clinical trials. Some side effects may differ depending on whether Rybrevant is given alone or in combination with lazertinib.

Side Effects When Given Alone (Subcutaneous)

Additional Side Effects When Used with Lazertinib

When Rybrevant is used in combination with lazertinib (either as IV infusion or subcutaneous injection), the following additional side effects have been reported:

Reporting Side Effects

Reporting suspected side effects after a medicine has been approved is important. It allows ongoing monitoring of the medicine's benefit-risk balance. Healthcare professionals and patients are encouraged to report any suspected adverse reactions to their national pharmacovigilance authority (e.g., the FDA in the United States, the EMA in Europe, or the MHRA in the United Kingdom).

How Should You Store Rybrevant?

Rybrevant must be stored in a refrigerator at 2-8°C (36-46°F). Do not freeze. Keep in the original packaging to protect from light. Once prepared in a syringe, it may be stored for up to 24 hours refrigerated, followed by up to 24 hours at room temperature (15-30°C). Rybrevant is stored and administered at the hospital or clinic.

Rybrevant will be stored and handled by the hospital or clinic where you receive treatment. However, understanding the storage requirements helps you appreciate the importance of proper medication handling. Key storage guidelines include:

• Temperature: Store in a refrigerator at 2°C to 8°C (36°F to 46°F)
• Do not freeze: Freezing may damage the medicine and alter its effectiveness
• Light protection: Keep in the original packaging to protect from light exposure
• Expiry date: Do not use after the expiration date printed on the carton and vial label
• Prepared syringe: Once drawn into a syringe, Rybrevant can be stored for up to 24 hours at 2-8°C, followed by up to 24 hours at room temperature (15-30°C)
• Single use only: Each vial is for single use. Any unused medicine must be discarded according to institutional guidelines

Keep all medicines out of the sight and reach of children. Do not dispose of medicines in wastewater or household waste. Your healthcare facility will dispose of unused medicine in an environmentally responsible manner.

What Does Rybrevant Contain?

Rybrevant contains the active substance amivantamab at a concentration of 160 mg per mL. It is available as a 10 mL vial (1,600 mg) and a 14 mL vial (2,240 mg). Inactive ingredients include recombinant human hyaluronidase (rHuPH20), disodium edetate, acetic acid, L-methionine, polysorbate 80, sodium acetate trihydrate, sucrose, and water for injections.

Active Ingredient

The active substance is amivantamab, a bispecific antibody produced using recombinant DNA technology. Each milliliter of solution contains 160 mg of amivantamab.

Inactive Ingredients (Excipients)

The other ingredients in Rybrevant include:

• Recombinant human hyaluronidase (rHuPH20): An enzyme that facilitates subcutaneous absorption of the medicine
• Disodium edetate (dihydrate): A stabilizer
• Concentrated acetic acid: A pH adjuster
• L-methionine: An antioxidant
• Polysorbate 80 (E433): A surfactant (0.6 mg per mL)
• Sodium acetate trihydrate: A buffer
• Sucrose: A stabilizer
• Water for injections: The solvent

Appearance

Rybrevant solution for injection is a colorless to slightly yellow liquid. It is supplied in glass vials within a cardboard carton. Do not use the medicine if it appears cloudy, discolored, or contains visible particles.

Marketing Authorization Holder

Rybrevant is manufactured by Janssen Biologics B.V. (Leiden, Netherlands) and marketed by Janssen-Cilag International NV (Beerse, Belgium), a subsidiary of Johnson & Johnson. The medicine has been approved by major regulatory authorities including the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA).