How does Rybrevant work?

Rybrevant is a targeted medicine that works at the epidermal growth factor receptor (EGFR) gene mutation and MET receptor found in certain types of non-small cell lung cancer (NSCLC). EGFR and MET are proteins that help cancer cells to grow. Targeting these proteins helps to slow down or stop cancer growth.

A mutation (change) in the gene for EGFR can make it grow and lead to cancer. This mutation is one change that your doctor may look for in NSCLC. Rybrevant also helps your immune system to identify cancer cells with EGFR and destroy them.

Rybrevant is considered a monoclonal antibody, which is an immune system protein made in the laboratory. It targets two proteins that fuel cancer cell growth: EGFR and MET and is considered a "bispecific" antibody.

What does Rybrevant treat?

Rybrevant (amivantamab-vmjw) can be used to treat NSCLC in four different ways:

• In combination with orally-administered Lazcluze (lazertinib) which is a tyrosine kinase inhibitor (TKI). In this setting it is used as first-line treatment of adults with NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations that cannot be removed by surgery or has spread.
• In combination with the chemotherapy medicines carboplatin and pemetrexed to treat NSCLC as a second-line treatment in patients with EGFR exon 19 deletions or exon 21 L858R substitution mutations whose disease has worsened on or after treatment with an EGFR tyrosine kinase inhibitor.
• In combination with chemotherapy (carboplatin and pemetrexed) as a first-line (initial) treatment for adults with EGFR-positive NSCLC (exon 20 insertion mutations) that cannot be removed by surgery or has spread to other parts of the body (metastatic).
• Alone (as a single medicine) in adults with EGFR-positive NSCLC (exon 20 insertion mutations) that cannot be removed by surgery or has spread to other parts of the body (metastatic), and has not responded to platinum-based chemotherapy.

Your doctor can perform a blood or tissue test (called a biomarker test) approved by the FDA to make sure the cancer has the specific EGFR mutation and you can receive Rybrevant.

How do I receive Rybrevant?

Rybrevant is either given alone, in combination with two chemotherapy drugs called pemetrexed and carboplatin, or with a kinase inhibitor called Lazcluze for the treatment of EGFR-positive NSCLC.

It is given as an intravenous (IV) infusion into your vein, usually in an infusion clinic. Your healthcare provider will determine your dose based on your body weight. You may receive medications before your infusion (antihistamines, fever-reducing medicines and steroids) to help prevent infusion-related reactions from your treatment. Your doctor will monitor you closely.

After the initial dosing schedule over the first 6 weeks, you will receive Rybrevant IV infusions either every 2 or 3 weeks. It is usually given until your disease worsens or you have side effects that require you to stop treatment.

Learn more: Dosing for Rybrevant (in more detail)

Is Rybrevant a chemo drug?

No, Rybrevant (amivantamab-vmjw) is not chemotherapy ("chemo"). It is a targeted drug treatment known as a bispecific EGF receptor-directed and MET receptor-directed antibody used to treat certain types of non-small cell lung cancer with an EGFR gene mutation. Because it binds to two proteins, it’s called a "bispecific" monoclonal antibody. A monoclonal antibody is a lab-made version of a specific immune system protein.

It targets two proteins that help cancer cells grow: EGFR and MET. It is not considered a chemotherapy or an immunotherapy, but is a targeted drug that works specifically at these mutations.

How long does Rybrevant work?

CHRYSALIS: Previously treated NSCLC with EGFR exon 20 insertion mutations

In the CHRYSALIS study looking at Rybrevant treatment alone (without chemotherapy), the median duration of response was 11.1 months, with 63% of people having a duration of response lasting 6 months or longer.

• The CHRYSALIS study included 81 patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations whose disease had progressed on or after platinum-based chemotherapy.
• In this population, the median age was 62, 59% were female and 53% of patients had never smoked, 46% had received prior immunotherapy and the median number of prior therapies was 2 (ranging from 1 to 7).
• Patients received Rybrevant monotherapy at 1050 mg once weekly for 4 weeks, then every 2 weeks thereafter until disease progression or unacceptable toxicity.
• The overall response rate (ORR) was 40%, with 3.7% of patients having a complete response* and 36% achieving a partial response. The median duration of response (DOR) was 11.1 months, with 63% of people having a duration of response lasting at least 6 months.

PAPILLON: First-line treatment of NSCLC with EGFR exon 20 insertion mutations

In the open-label, Phase 3 PAPILLON study of Rybrevant for first-line treatment of NSCLC with EGFR exon 20 mutations, the median duration of response (DOR) was 10.1 months in the group receiving Rybrevant plus chemotherapy, compared to 5.6 months in the group receiving chemotherapy alone.

• The PAPILLON study included 308 patients with previously untreated locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations.
• Participants received IV infusions of Rybrevant in combination with chemotherapy (carboplatin and pemetrexed) or chemotherapy alone. Dosing is outlined in the product information. In this population, the median age was 62, 58% were female, 58% of patients had never smoked, and 84% had Stage IV cancer at initial diagnosis.
• The primary efficacy outcome measure was progression-free survival (PFS). Rybrevant + chemotherapy demonstrated a statistically significant improvement in PFS for patients in the Rybrevant + chemotherapy group (11.4 months) compared to those receiving only chemotherapy (6.7 months). Rybrevant plus chemotherapy resulted in a 61% reduction in the risk of disease progression or death compared to chemotherapy alone.
• The overall response rate (ORR) was 67% in the Rybrevant + chemotherapy vs. 36% with chemotherapy alone (with a 4% complete response* and a 63% partial response in the Rybrevant + chemotherapy group).
• The median duration of response (DOR) was 10.1 months in the Rybrevant + chemotherapy group, compared to 5.6 months in those receiving chemotherapy alone.

Related questions

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MARIPOSA: EGFR exon 19 deletions or substitution mutations

The MARIPOSA Phase 3 study enrolled 1,074 patients to look at Rybrevant used with Lazcluze compared to osimertinib (Tagrisso) used alone and Lazcluze used alone (an unapproved treatment for NSCLC) for first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or substitution mutations.

Patients received treatment until the cancer worsened or they had unacceptable toxicity.

The primary endpoint of the study was progression free survival (PFS). PFS is the length of time during and after the treatment of the cancer that a patient lives with the disease but it does not get worse.

Results from the MARIPOSA study showed Rybrevant plus Lazcluze reduced the risk of disease progression or death by 30% compared to osimertinib (Tagrisso) with a median progression-free survival (PFS) of 23.7 months (versus 16.6 months) in the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations.

The median duration of response (DOR) was nine months longer with Rybrevant plus Lazcluze versus osimertinib (25.8 months versus 16.7 months), a secondary endpoint of the study.
The overall response rate (ORR) was found to be 78% in patients receiving Rybrevant plus Lazcluze (5.4% complete response) and 73% for those receiving osimertinib (3.5% complete response).

MARIPOSA-2: EGFR ex19del or L858R substitution mutations with disease worsening on or after receiving osimertinib (Tagrisso)

Researchers found statistically significant progression-free survival (PFS) benefits, the primary endpoint, in the Phase 3 MARIPOSA-2 study. Progression-free survival is the length of time during and after the treatment of the cancer that a patient lives with the disease but it does not get worse.

In MARIPOSA-2 researchers looked at the effectiveness and safety of Rybrevant in combination with the platinum chemotherapy agents carboplatin and pemetrexed compared to patients receiving only the chemotherapy drugs. These regimens were used in treatment of 394 adults with NSCLC with EGFR ex19del or L858R substitution mutations whose disease has worsened on or after treatment with an EGFR tyrosine kinase inhibitor called osimertinib (Tagrisso).

Results showed Rybrevant plus chemotherapy reduced the risk of disease progression or death (progression-free survival [PFS]) by 52% vs. chemotherapy alone (74 events vs. 171). The median PFS (time during and after the treatment of the cancer that a patient lives with the disease but it does not get worse) for patients receiving Rybrevant plus chemotherapy was 6.3 months, compared to 4.2 months for chemotherapy alone.

Additionally, Rybrevant plus chemotherapy showed a significant overall response rate (ORR) of 53% compared to 29% with chemotherapy alone. This was a key secondary endpoint. In a clinical trial, measuring the ORR is one way to see how well a new treatment works. The ORR is the percent of people who partially or completely respond to treatment over a period of time. A partial response means that the tumor has decreased in size, and a complete response means there is a disappearance of all signs of cancer in the body at that time.

There was a numerical but not a significant difference seen in the overall survival (OS) between the 2 groups when evaluated at the pre-specified time point. OS is the length of time from the start of treatment that the patient is still alive. The median OS was 17.7 months in the group that received Rybrevant plus chemotherapy, and 15.3 months in the group that received only chemotherapy.

Note: It's important to know that the disappearance of all signs of cancer in response to treatment (complete response) does not always mean the cancer has been cured.

What side effects can occur with Rybrevant?

Before you start treatment, discuss all possible side effects with your doctor.

Rybrevant may cause serious side effects such as infusion-related reactions, interstitial lung disease / pneumonitis, severe skin reactions, and eye problems.

Common side effects when Rybrevant is used alone include rash, muscle and joint pain, infusion reactions, nail infections, shortness of breath, constipation, cough, fatigue, edema, stomatitis (mouth sores), and nausea and vomiting.

When Rybrevant is given with chemotherapy, common side effects include: rash, nail toxicity, stomatitis (mouth sores), infusion reactions, fatigue, edema (fluid build-up), muscle pain, constipation, decreased appetite, nausea, COVID-19, diarrhea, and vomiting.

When Rybrevant is given with Lazcluze (lazertinib) common adverse reactions (≥ 20%) were rash, nail toxicity, infusion-related reaction, muscle and bone pain, stomatitis (mouth sores), edema, venous thromboembolism (blood clot formation), paresthesia (tingling feeling in hands, feet), fatigue, diarrhea, constipation, COVID-19, hemorrhage, dry skin, decreased appetite, pruritus (itching), nausea and ocular toxicity.

Laboratory abnormalities may also occur, for example: changes in red or white blood cells counts, changes in electrolytes (like sodium or potassium), and changes in tests that evaluate your liver.

Related: Rybrevant side effects (in more detail)

This is not all the information you need to know about Rybrevant (amivantamab-vmjw) for safe and effective use and does not take the place of your healthcare provider's directions. Review the full product information and discuss this information and any questions you have with your doctor or other health care provider.