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 19 deletion or exon 21 L858R substitution mutations

About the medicinal product

Rybrevant is a cancer treatment containing the active substance amivantamab.

Swissmedic first authorised Rybrevant temporarily on 20 January 2022. At the time, Rybrevant was authorised as monotherapy (treatment with just one medicinal product) for patients with non-small-cell lung cancer (NSCLC) with activating exon 20 gene mutations whose cancer had progressed during or after platinum-based chemotherapy (i.e. as second-line treatment). In the meantime, the associated conditions of authorisation have been fulfilled and the temporary authorisation has been lifted.

Under this indication extension, Rybrevant can be used in combination with lazertinib as first-line treatment in adults with NSCLC with EGFR exon 19 deletion or exon 21 L858R substitution mutations.

Rybrevant is suitable for treating patients in whom a specific change (mutation) has been detected in the gene for the epidermal growth factor receptor^[1] (EGFR) before treatment begins. These gene changes are called exon 20 insertion mutations, exon 19 deletion mutations or exon 21 L858R substitution mutations of the EGFR gene.

This indication extension for Rybrevant was authorised under Project Orbis. Project Orbis is a programme for promising cancer treatments coordinated by the FDA, the US regulatory authority. It provides a framework for the concurrent submission and review of cancer medicines by several international partner authorities in various countries. The ultimate aim is to give patients faster access to innovative cancer treatments. In addition to the FDA, the authorisation authorities in Australia (TGA), Brazil (ANVISA), Canada (HC), Israel (MOH), Singapore (HSA), Switzerland (Swissmedic), and the United Kingdom (MHRA) are currently represented in Project Orbis.

^[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). In its newly authorised indication, Rybrevant is used in combination with lazertinib.

Rybrevant can only be used if the specific EGFR exon 19 deletion or exon 21 L858R substitution mutations have been detected.

The recommended dose for the new indication is determined by the patient's weight, and is 1,050 mg up to 80 kg and 1,400 mg above 80 kg body weight. Patients receive one dose a week in weeks 1 to 5. They do not receive any Rybrevant in week 6, then receive it once every two weeks from week 7.

Rybrevant is administered by a healthcare professional.

Efficacy

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

The study compared the combination of Rybrevant and lazertinib with osimertinib monotherapy as first-line treatment.

A total of 858 patients with advanced or metastatic non-small-cell lung cancer (NSCLC) with EGFR exon 19 deletion or exon 21 L858R substitution mutations took part.

The study showed a significant improvement in progression-free survival (PFS)^[2] in patients who had received Rybrevant in combination with lazertinib (23.7 months) compared with patients who had received osimertinib monotherapy (16.6 months).

In addition, overall survival (OS) was significantly improved in patients who had been treated with Rybrevant and lazertinib compared with patients who had received osimertinib on its own.

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.}

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)^[3].

There is also a risk of interstitial lung disease (ILD)^[4] and skin reactions such as toxic epidermal necrolysis (TEN)^[5].

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

^[3] _{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}

^[4] _{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.}

^[5] _{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 treatment options for patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) with EGFR exon 19 deletion or exon 21 L858R substitution mutations.

The study described above showed a significant improvement in progression-free survival and overall survival for combination treatment with Rybrevant and lazertinib compared with existing options for the first-line treatment of patients with NSCLC and EGFR exon 19 deletion or exon 21 L858R substitution mutations, such as osimertinib combined with chemotherapy.

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 19 deletion or exon 21 L858R substitution mutations.

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.}