Rybrevant Faspro: FDA Approves Once-Monthly Dosing in Combination With Lazcluze for EGFR-Mutated Lung Cancer

Rybrevant Faspro is an under-the-skin (subcutaneous, or SC) injection form of the anticancer medicine Rybrevant (amivantamab). The FDA has approved a new monthly dosing option for Rybrevant Faspro to be used in combination with the oral drug lazertinib (Lazcluze) as the first‑line treatment for people with advanced non‑small-cell lung cancer (NSCLC) who have certain genetic changes (mutations) in the epidermal growth factor receptor (EGFR) gene.

Lung cancer is one of the most common cancers globally, with NSCLC accounting for 80%-85% of the cases. Some NSCLC tumors have mutations in the EGFR gene, which promote unchecked growth of cancer cells. These mutations are found in 10%-15% of Western patients and in 40%-50% of Asian patients and are commonly seen in younger people who are nonsmokers. EGFR exon 19 deletions and L858R mutations are the most common mutations, while exon 20 insertions occur less frequently but are more aggressive. These EGFR mutations are linked to poor clinical outcomes as survival remains low: About 20% of people with advanced NSCLC and EGFR mutations live five years, and only 8% of those with exon 20 insertions vs 19% of those with exon 19 or L858R mutations survive five years.

Rybrevant Faspro is an SC injection that combines two ingredients: amivantamab and hyaluronidase. Amivantamab is a first-in-class fully human lab-made bispecific antibody that selectively targets cancer cells with EGFR and mesenchymal-epithelial transition (MET) gene mutations, blocking cancer cell growth signals and helping your immune system identify and kill tumor cells. The recombinant hyaluronidase improves the medicine’s absorption when it is injected under the skin. Lazcluze is an oral targeted anticancer medicine that selectively blocks faulty EGFR signals and helps slow or stop the spread of cancer cells.

This approval is significant because it provides patients with a more convenient once-monthly treatment plan that matches the effectiveness and safety of the previous twice‑monthly plan while reducing clinic visits and simplifying care.

Why Was It Approved?

The FDA’s approval of the once-monthly dosing schedule for Rybrevant Faspro is supported by clinical data showing that it is as safe and effective as the previously approved every-two-weeks schedule, when given with Lazcluze as the first-line treatment for advanced EGFR-mutated NSCLC.

Patients in studies were able to switch to monthly dosing as early as week five and still achieved consistent outcomes, compared with the biweekly SC injections. And data presented from other studies showed a high objective response rate with monthly dosing. (A large percentage of patients saw their tumors shrink by a measurable amount or disappear completely after treatment.) Results also showed that once-monthly subcutaneous Rybrevant Faspro achieved the same average medicine levels in the blood as the intravenous (IV) and the biweekly SC injection forms.

The rate of administration-related reactions (ARR) with once-monthly SC treatment stayed about the same with the biweekly SC dosing schedule (12% vs. 13%) and was much lower than observed in older IV studies (66%). Also, blood clot events with once-monthly SC were similar with the biweekly SC (13% vs. 11% when patients were on blood thinners) and lower than older IV data in patients not using blood thinners (38%). Only 8% of patients stopped treatment because of side effects, and overall safety was similar to that of established treatment plans.

Rybrevant Faspro in combination with Lazcluze may cause common side effects, including skin rashes, nail problems, muscle or joint pain, fatigue, mouth sores, swelling (edema), nausea, diarrhea, vomiting, constipation, loss of appetite, and headaches. Blood tests may also show changes like low white blood cell and platelet counts; low levels of sodium, potassium, albumin, or hemoglobin; and higher levels of liver enzymes.

What Do I Need to Know?

Rybrevant Faspro is given by a health care provider as an injection under the skin, usually in the belly, and takes about five minutes to give. Your health care provider will decide your dosing schedule depending on your weight and treatment plan. Adult patients receiving IV amivantamab every two weeks may switch to SC Rybrevant Faspro every two or four weeks starting from their scheduled dose on or after week five. Those receiving IV amivantamab every three weeks may switch to SC Rybrevant Faspro every three weeks on or after week four. Patients already receiving Rybrevant Faspro every two weeks may transition to once-monthly (every four weeks) beginning on or after week five.

If you miss an appointment, contact your health care provider right away to reschedule it.

Before each dose, your health care provider may give you other medicines to help prevent allergic reactions, skin and nail reactions, or injection-related side effects. If you’re also taking Lazcluze, take your Lazcluze pill by mouth before your Rybrevant Faspro injection. Your health care provider may give you blood thinners for the first four months of treatment to reduce the risk of blood clots.

As Rybrevant Faspro can cause skin reactions, you should limit your sun exposure during and for two months after your treatment. Use a broad-spectrum sunscreen and wear protective clothing while out in the sun. During your treatment, use a skin moisturizer that does not clog your pores or contain drying ingredients and offers long-lasting skin hydration on your face and whole body (except the scalp). Wash your hands and feet every day with 4% chlorhexidine solution.

You should not use Rybrevant Faspro if you’re allergic to hyaluronidase or any of the ingredients. Tell your health care provider about all your health conditions, including liver, skin, or eye problems, and especially about any lung or breathing problems other than cancer. Let your provider know about any other medicines you take – including over-the-counter products, vitamins, supplements, or herbal remedies – and especially about those that affect liver enzymes, because lazertinib may interact with them.

If you’re pregnant or breastfeeding, you should avoid this medicine, as it may harm your fetus. Use birth control and avoid breastfeeding during treatment and for three months after your last dose.

Contact your health care provider right away if you have a fever; sweating or chills; coughing or trouble breathing; dizziness; swelling; leg pain or tenderness; unexplained chest pain; a rash; redness; itching; blisters; painful sores; raised acne-like bumps; dry skin; red, itchy, or dry eyes; blurred vision; inflammation of the eyelids; or sensitivity to light. These could be signs of serious side effects.