Rybrevant Faspro

Rybrevant Faspro is used to treat non-small cell lung cancer (NSCLC) in adults that has spread to other parts of the body (metastatic) or cannot be removed by surgery, and has certain abnormal epidermal growth factor receptor (EGFR) gene(s):

• In combination with lazertinib as a first-line treatment
• In combination with carboplatin and pemetrexed for people whose disease has worsened on or after treatment with an EGFR tyrosine kinase inhibitor (TKI)
• In combination with carboplatin and pemetrexed as a first-line treatment
• Alone in people whose disease has worsened on or after platinum-based chemotherapy.

Your healthcare provider will perform a test to make sure that Rybrevant Faspro is right for you.

Rybrevant Faspro is a subcutaneous injection that is quicker to administer than Rybrevant intravenous infusion and reduces the incidence of administration reactions 5-fold.

Rybrevant Faspro gained FDA approval on December 17, 2025.

Rybrevant Faspro will be given to you by your healthcare provider as an injection under the skin (subcutaneous injection), in the stomach area (abdomen).

• Rybrevant Faspro is injected over about 5 minutes for each injection.
• Your healthcare provider will decide the time between doses as well as how many treatments you will receive.
• Your healthcare provider will give you medicines before each dose of Rybrevant Faspro to help reduce the risk and severity of allergic and injection-related reactions.
• Your healthcare provider may give you medicines in addition to Rybrevant Faspro to reduce the risk and severity of skin and nail reactions.

Rybrevant Faspro may be given in combination with the medicines carboplatin and pemetrexed. If you have any questions about these medicines, ask your healthcare provider.

If your treatment with Rybrevant Faspro is given in combination with the medicine lazertinib, you should take your dose of lazertinib by mouth anytime before your injection with Rybrevant Faspro.

Do not receive Rybrevant Faspro if you are allergic to hyaluronidase or any of the ingredients in Rybrevant Faspro.

Before you receive Rybrevant Faspro, tell your healthcare provider about all of your medical conditions, including if you:

• Have a history of lung or breathing problems, other than cancer
• Are pregnant or plan to become pregnant
• Are breastfeeding or plan to breastfeed.

It is not known if Rybrevant Faspro is safe and effective in children.

Pregnancy

Rybrevant Faspro can harm your unborn baby. Females who can become pregnant:

• Your healthcare provider should do a pregnancy test before you start treatment with Rybrevant Faspro.
• You should use effective birth control (contraception) during treatment and for 3 months after your last dose of Rybrevant Faspro.
• Tell your healthcare provider right away if you become pregnant or think you might be pregnant during treatment with Rybrevant Faspro.

Breastfeeding

It is not known if Rybrevant Faspro passes into your breast milk. Do not breastfeed during treatment and for 3 months after your last dose of Rybrevant Faspro.

Common side effects

The most common side effects of Rybrevant Faspro are:

• Rash
• Infected skin around the nail
• Muscle and joint pain
• Feeling very tired
• Sores in the mouth
• Swelling of hands, ankles, feet, face, or all of your body
• Nausea
• Diarrhea
• Vomiting
• Constipation
• Decreased appetite
• Headache
• Changes in certain blood tests.

Side effects of Rybrevant IV infusion that may occur with Rybrevant Faspro injection include:

• Infusion-related reactions
• Unusual skin sensations (e.g., tingling)
• Dry skin and itching
• Shortness of breath and cough
• Bleeding
• COVID-19.

Serious side effects

Rybrevant Faspro may cause the following serious side effects:

• Allergic and injection-related reactions: These are common and can be severe or serious. Tell your healthcare provider right away if you get any of the following symptoms during or after your injection of Rybrevant Faspro: Shortness of breath Fever Chills Flushing Chest discomfort Dizziness or lightheadedness Vomiting
• Lung problems. Rybrevant Faspro can cause lung problems that can lead to death. Symptoms may be similar to those symptoms from lung cancer. Tell your healthcare provider right away if you get any new or worsening lung symptoms, including: Shortness of breath Cough Fever.
• Blood clot problems. Rybrevant Faspro, when given in combination with lazertinib, can cause blood clots in the veins of your legs (deep vein thrombosis) or lungs (pulmonary embolism) that can lead to death. Your healthcare provider may start you on medicine to prevent blood clots for the first 4 months of treatment. Tell your healthcare provider right away if you get any signs and symptoms of blood clots, including: Swelling, pain, or tenderness in the leg Sudden unexplained chest pain Shortness of breath
• Skin problems. Rybrevant Faspro can cause severe rash, including blisters, peeling, skin pain and sores, redness, raised acne-like bumps, itching, and dry skin. Your healthcare provider may start you on an antibiotic for the first 3 months of treatment, followed by an antibiotic lotion for your scalp for the next 9 months. During treatment with Rybrevant Faspro, you should apply a non-comedogenic (does not clog pores) skin moisturizer (ceramide-based or other types of moisturizers that provide long-lasting skin hydration and do not include drying ingredients) on your face and whole body (except scalp) and wash your hands and feet every day with 4% chlorhexidine solution. Tell your healthcare provider right away if you get any skin reactions. Your healthcare provider may treat you with a medicine(s) or send you to see a skin specialist (dermatologist) if you get skin reactions during treatment with Rybrevant Faspro.
• Eye problems. Rybrevant Faspro can cause eye problems. Tell your healthcare provider right away if you get symptoms of eye problems, which may include: Eye pain Inflammation of the eyelids Dry eyes Eye redness Blurred vision Changes in vision Itchy eyes Excessive tearing Sensitivity to light.

Your healthcare provider may send you to see an eye specialist (ophthalmologist) if you get new or worsening eye problems during treatment with Rybrevant Faspro. You should not use contact lenses until your eye symptoms are checked by a healthcare provider.

These are not all of the possible side effects of Rybrevant Faspro. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Rybrevant Faspro (amivantamab/hyaluronidase) works by targeting EGFR and MET, disrupting their signaling by blocking ligand binding and promoting receptor degradation. It also directs immune effector cells to destroy tumor cells via ADCC and trogocytosis. Co-formulated hyaluronidase transiently depolymerizes hyaluronan in subcutaneous tissue, temporarily enhancing permeability to facilitate drug delivery, with tissue permeability restored within 24 to 48 hours.

Rybrevant Faspro belongs to the drug class called combination bispecific antibodies with endoglycosidases.

Dose of Rybrevant Faspro in Combination with Carboplatin and Pemetrexed (Every 3 Week Dosing)

Rybrevant Faspro is given every 3 weeks with carboplatin and pemetrexed until disease progression or unacceptable toxicity.

Dosing by body weight:

• Under 80 kg: 1,600 mg amivantamab/20,000 units hyaluronidase (Week 1, Day 1), then 2,400 mg amivantamab/30,000 units hyaluronidase weekly (Weeks 2-3 on day 1, then every 3 weeks starting at week 4 onwards)
• 80 kg or more: 2,240 mg amivantamab/28,000 units hyaluronidase (Week 1, Day 1), then 3,360 mg amivantamab and 42,000 units hyaluronidase weekly (Weeks 2-3 on day 1, then every 3 weeks starting at week 4 onwards)

Administration order: Pemetrexed first, carboplatin second, Rybrevant Faspro last. Carboplatin continues for up to 12 weeks; pemetrexed continues until progression.

Dose of Rybrevant Faspro in Combination with Lazertinib or as a Single Agent (Every 4-Week Dosing)

Under 80 kg:

• Weeks 1 to 4: 1,600 mg amivantamab/20,000 units hyaluronidase weekly (total of 4 doses) (Injection on Day 1)
• Week 5 onwards: 3,520 mg amivantamab/44,000 units hyaluronidase every 4 weeks

≥ 80 kg:

• Weeks 1 to 4: 2,240 mg amivantamab/28,000 units hyaluronidase weekly (total of 4 doses) (Injection on Day 1)
• Week 5 onwards: 4,640 mg amivantamab/58,000 units hyaluronidase every 4 weeks

Dose of Rybrevant Faspro in Combination with Lazertinib or as a Single Agent (Every 2-Week Dosing)

Under 80 kg:

• Weeks 1 to 4: 1,600 mg amivantamab/20,000 units hyaluronidase weekly (total of 4 doses) (Injection on Day 1)
• Week 5 onwards: 1,600 mg amivantamab/20,000 units hyaluronidase every 2 weeks*

≥ 80 kg:

• Weeks 1 to 4: 2,240 mg amivantamab/28,000 units hyaluronidase weekly (total of 4 doses) (Injection on Day 1)
• Week 5 onwards: 2,240 mg amivantamab/28,000 units hyaluronidase every 2 weeks*

* May switch to Rybrevant Faspro every 4-week dosing regimen at their next scheduled dose on or after Week 5.

Premedications

Administer the following premedications before a Rybrevant Faspro injection to reduce the risk of administration-related reactions:

• Antihistamine (diphenhydramine 25-50 mg or equivalent) IV: 15-30 minutes before dose Oral: 30-60 minutes before dose Required before all doses
• Antipyretic (acetaminophen 650-1,000 mg or equivalent) IV: 15-30 minutes before dose Oral: 30-60 minutes before dose Required before all doses
• Glucocorticoid (dexamethasone 20 mg or 10 mg, depending on protocol) IV: 45-60 minutes before dose Oral: 60-90 minutes before dose Required at Week 1 Day 1, upon reinitiation after interruptions, and as needed for subsequent injections.

If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment.

Rybrevant Faspro can cause skin reactions. You should limit your time in the sun during and for 2 months after your treatment with Rybrevant Faspro. Wear protective clothing and use broad-spectrum sunscreen during treatment with Rybrevant Faspro.

Active ingredient: amivantamab and hyaluronidase-lpuj

Inactive ingredients: edetate disodium, glacial acetic acid, methionine, polysorbate 80, sodium acetate, sucrose, and Water for Injection.

Manufactured by: Janssen Biotech, Inc., Horsham, PA 19044, USA. U.S. License Number 1864 and Halozyme, Inc., San Diego, CA 92130, USA. U.S. License Number 2187.