Concentrate for solution for infusion for the first-line treatment of adults with locally advanced or metastatic non-small-cell lung cancer (NSCLC) with EGFR exon 20 insertion mutation

About the medicinal product

Rybrevant is a cancer treatment containing the active substance amivantamab.

Swissmedic first authorised Rybrevant temporarily on 20 January 2022 for the treatment of non-small-cell lung cancer (NSCLC) with activating exon 20 gene mutations. In the meantime, the associated conditions of authorisation have been fulfilled and the temporary authorisation has been lifted.

As a result of this indication extension, Rybrevant can be used for the first-line treatment of adult NSCLC patients whose cancer is locally advanced or has spread to other parts of the body (metastatic) in combination with the chemotherapy agents carboplatin, and pemetrexed.

Before treatment can begin, however, patients must be tested to confirm that they have a specific change (mutation) in the epidermal growth factor receptor^[1] (EGFR) gene. This gene mutation is termed an exon 20 insertion mutation of the EGFR gene.

^[1] _{A receptor is a protein or a protein complex located on the surface of, or inside, cells. When a specific substance binds to a receptor, a reaction is triggered in the cell.}

Mode of action

The active substance of Rybrevant is amivantamab. Amivantamab is an antibody that binds specifically to two receptors (targets) on the surface of cancer cells. These receptors, known as EGFR and MET, are often present and changed in non-small-cell lung cancer. By blocking the signals from these receptors, amivantamab can stop the growth and replication of the cancer cells. In addition, the active substance helps the immune system identify and combat the cancer cells. This slows or stops the growth of the tumours.

Administration

Rybrevant is a prescription-only medicine authorised as a concentrate for solution for infusion at the dosage strength of 350 mg / 7 ml. It is administered intravenously (into the veins). Rybrevant is used in combination with carboplatin and pemetrexed.

Rybrevant can only be used if the specific EGFR exon 20 insertion mutation has been detected.

The recommended dose for the new indication depends on the patient's weight, i.e. 1,400 mg up to 80 kg and 1,750 mg above 80 kg body weight. Patients receive one dose a week in weeks 1 to 4. After that, Rybrevant is administered every three weeks until the disease progresses or the patient experiences intolerable side effects.

Rybrevant is administered by a healthcare professional.

Efficacy

The efficacy of Rybrevant in the present indication extension was investigated in the PAPILLON study.

The study compared a combination of the active substance in Rybrevant (amivantamab), carboplatin, and pemetrexed (ACP) with a combination of carboplatin and pemetrexed (CP) on their own. Carboplatin and pemetrexed are chemotherapy medications used as standard treatments for NSCLC.

A total of 308 patients with advanced or metastatic NSCLC with EGFR exon 20 insertion mutation took part.

This study showed a significant improvement in progression-free survival (PFS)^[2] in the ACP group compared with the CP group. Median^[3] PFS was 11.4 months in the ACP group compared with 6.7 months in the CP group.

The data currently available from the ongoing study do not show any significant improvement in overall survival. Overall survival refers to the period between the start of treatment and the death of the patient.

^[2] _{PFS: progression-free survival. Period between the start of a treatment or a clinical trial and the onset of disease progression or the death of the patient.}

^[3] _{Median: The value that lies exactly in the middle of a distribution of data is called the median or central value. Half of the data values are always less than the median, the other half are always greater.}

Precautions, undesirable effects & risks

Rybrevant must not be used in those who are hypersensitive to the active substance amivantamab.

The most common undesirable effects include infusion-related reactions, rash, and nail disorders.

Other side effects include nausea, fatigue, reduced appetite, and venous thromboembolic events (VTE)^[4].

There is also a risk of interstitial lung disease (ILD)^[5] and skin reactions such as toxic epidermal necrolysis (TEN)^[6].

All precautions, risks, and other possible undesirable effects are listed in the Information for healthcare professionals.

^[4] _{Venous thromboembolic events (VTE) can be life-threatening and are associated with blood clots that form in the veins and may cause pulmonary embolism or deep vein thrombosis.}

^[5] Interstitial lung disease (ILD) is a group of lung diseases characterised by inflammation and scarring of the lung tissue that can cause respiratory symptoms and restricted oxygen absorption.

^[6] _{Toxic epidermal necrolysis (TEN) is a rare but serious skin disease involving extensive blistering and peeling of the top layer of skin.}

Why the medicinal product has been authorised

At present, there are only limited first-line drug treatment options for patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) with EGFR exon 20 insertion mutation.

The study described above shows that Rybrevant in combination with carboplatin and pemetrexed offers significantly improved progression-free survival.

Taking all the risks and precautions into account, and based on the available data, the benefits of Rybrevant outweigh the risks. Swissmedic has therefore authorised the indication extension for Rybrevant in Switzerland for the treatment of advanced or metastatic NSCLC with EGFR exon 20 insertion mutation.

Further information on the medicinal product

Information for healthcare professionals:

Healthcare professionals can answer any further questions.

^{The date of revision of this text corresponds to that of the SwissPAR. New information concerning the authorised medicinal product in question will not be incorporated into the Summary report on authorisation.}

^{Swissmedic monitors medicinal products authorised in Switzerland. Swissmedic initiates the necessary action in the event of newly discovered adverse drug reactions or other safety-relevant signals. New findings that could impair the quality, efficacy, or safety of this medicinal product are recorded and published by Swissmedic. If necessary, the medicinal product information is adapted.}