How do Exkivity and Rybrevant compare for NSCLC?

Official answer

by Drugs.com

Key Points

What are Exkivity and Rybrevant used for?

Exkivity (mobocertinib) and Rybrevant (amivantamab-vmjw) are both targeted prescription medicines approved by the FDA to treat adults with locally advanced or metastatic non-small cell lung cancer (mNSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test.

Rybrevant from Janssen was first approved by the FDA in May 2021, and Exkivity, manufactured by Takeda Pharmaceuticals, was approved in September 2021.

Both drugs are approved by the FDA under “accelerated approval” based on how many patients responded and how long they responded.

What are NSCLC with EGFR exon 20 insertion mutations?

NSCLC with epidermal growth factor receptor (EGFR) exon 20 insertion mutations are a certain type of mNSCLC with genetic mutations. Exon 20 mutations can allow cancers to grow and spread.

EGFR exon 20 insertion mutation is a protein biomarker. Biomarkers occur in tissues, blood and other bodily fluids and can help identify what type of cancer mutation you might have. Your doctor can order a special test to identify these mutations. Identifying an exon 20 insertion mutation will allow your doctor to select a more specific type of drug treatment for this cancer.

NSCLC with epidermal growth factor receptor (EGFR) exon 20 insertion mutations are typically resistant to treatment with conventional targeted EGFR tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors used alone.

While NSCLC is the most common type of lung cancer, mNSCLS with epidermal growth factor receptor (EGFR) exon 20 insertion mutations are rare, occurring in about 2000 to 4000 patients each year, but many patients may go undiagnosed because they do not get the kind testing they need.

These types of mutations can occur in patients who smoke, previously smoked, or never smoked. Typical survival time after diagnosis of metastatic NSCLC with EGFR exon 20 insertion mutations is a median of 16.2 months. The five-year survival rate for exon 20 insertion mutations is 8%.

How do Exkivity and Rybrevant work in NSCLC?

Both Exkivity and Rybrevant target EGFR Exon 20 insertion mutations.

Exkivity is classified as an oral kinase inhibitor. Kinases are enzymes that affect different cell functions and may promote growth. It is the first oral therapy specifically designed to target EGFR Exon 20 insertion mutations. Exkivity inhibits (blocks) and irreversibly binds to EGFR Exon 20 insertion mutations to slow lung cancer growth.

Rybrevant is a targeted antibody treatment given by intravenous (IV) infusion. It is classified as a fully-human bispecific antibody directed against EGFR and MET receptors. It's called a bispecific antibody because it binds to two proteins that promote cancer growth: EGFR and MET. Rybrevant stops tumor growth by directly blocking these receptors on the cell surface.

How are Exkivity and Rybrevant given?

Exkivity is given as oral capsules taken by mouth. Rybrevant is given as an intravenous (IV) infusion.

Doses may need to be adjusted for either medicine, or treatment may need to be temporarily or permanently stopped, based on any serious side effects or drug interactions you may encounter. You will typically receive these medicines until your disease worsens or you have unacceptable side effects.

Before you receive a Rybrevant infusion, you will take premedications to help with any infusion-related side effects, such as shortness of breath, flushing, fever, chills, nausea, chest discomfort, hypotension, and vomiting. These premedications may include antihistamines like diphenhydramine (Benadryl), a fever reducer like acetaminophen (Tylenol) and an antiinflammatory medicine like dexamethasone or methylprednisolone.

What do studies say about Exkivity and Rybrevant effectiveness?

There are no head-to-head comparative studies of Exkivity to Rybrevant, so it is not possible to say if one is better than the other. Consult with your oncologist and cancer team to learn about these options and which treatment may be best for your particular situation.

Exkivity: Study 101

Approval for Exkivity was based on a study known as Study 101 submitted to the FDA. It included 114 patients with advanced or metastatic non-small cell lung cancer (NSCLC) that could not be removed by surgery or had spread to other parts of the body. These patients exhibited EGFR exon 20 insertion mutations, as determined by a special FDA-approved test.

Patients who could enroll in the study had received a chemotherapy treatment that contained platinum, but their lung cancer was worsening. In the study, patients received a 160 mg oral dose of Exkivity once daily until their lung cancer worsened or they had side effects they could not tolerate.

The effectiveness of Exkivity was determined by looking at the overall response rate (ORR) and the duration of response (DoR). The ORR looks at how many people using Exkivity saw a tumor response like shrinkage. The DoR measures how long the response lasted.

Rybrevant: CHRYSALIS study

Approval for Rybrevant was based on the Phase 1 CHRYSALIS study. This study included 129 patients with advanced or metastatic non-small cell lung cancer (NSCLC) that could not be removed by surgery or had spread to other parts of the body. These patients also exhibited EGFR exon 20 insertion mutations, as determined by testing.

Enrolled patients had received a chemotherapy treatment that contained platinum, but their mNSCLC was worsening. In the study, patients received intravenous Rybrevant dosing based on their weight. Patients weighing less than 80 kg (176 lbs) received a 1050 mg dose, and people 80 kg or over received a 1,400 mg dose. Treatment was given once weekly for 4 weeks, then every 2 weeks thereafter, until their lung cancer worsened or they had side effects they could not tolerate.

The effectiveness of Rybrevant was determined by looking at the overall response rate (ORR) and the duration of response (DoR). The ORR looks at how many people using Rybrevant saw a tumor response like shrinkage. The DoR measures how long the response lasted.

What are the common side effects with Exkivity and Rybrevant?

Side effects occur with most drugs but people do not usually experience all of the side effects listed. It is important to talk with your doctor about the symptoms of possible serious and common side effects, and understand what action you need to take if you experience one. The following is not a complete list of the possible side effects with Exkivity or Rybrevant.

Common side effects

Exkivity and Rybrevant have some side effects that are similar and some that are different.

Both Exkivity and Rybrevant can commonly cause (in greater than 20% of patients) the following side effects:

In studies, Exkivity was also shown to commonly cause diarrhea, decreased appetite, and dry skin in at least 20% of patients.

Rybrevant was also reported to commonly cause infusion-related reactions, shortness of breath, edema (fluid retention, swelling) cough, and constipation in at least 20% of patients.

Both Exkivity and Rybrevant can also lead to laboratory abnormalities like decreased white blood cells, changes in electrolytes, and decreases in potassium, among other laboratory value changes.

Serious side effects

Exkivity labeling carries a Boxed Warning for QTc prolongation and Torsades de Pointes (types of dangerous heart rhythms), plus warnings for heart toxicity, interstitial lung disease / pneumonitis and diarrhea that may lead to dehydration. Exkivity can also cause harm to an unborn baby.

Rybrevant may cause serious side effects such as infusion-related reactions, interstitial lung disease / pneumonitis, serious skin reactions, and eye problems. Rybrevant can also cause harm to an unborn baby.

Are Exkivity or Rybrevant recommended in cancer guidelines?

Yes, Exkivity and Rybrevant are both recommended as therapies for EGFR 20 Insertion Mutation positive NSCLC, according to the latest National Comprehensive Cancer Network (NCCN) guidelines dated March 16, 2022 (version 3.2022), in patients with worsening disease after initial treatment with platinum-based chemotherapy.

Which is more expensive, Exkivity or Rybrevant?

Like most cancer treatments, both Exkivity and Rybrevant are expensive. However, most people do not pay these full prices. Your insurance may help pay for your treatments, or the manufacturer may be able to offer financial assistance. Neither drug is available as a generic option.

Prices are for cash paying customers only and are not valid with insurance plans. Prices are based on using the Drugs.com discount card which is accepted at most U.S. pharmacies.

For questions regarding Exkivity costs and payment assistance, contact Takeda Pharmaceuticals at Takeda Oncology Here2Assist at 1-844-817-6468, select Option 2, Monday – Friday, 8:00 AM to 8:00 PM ET, or online.

For questions regarding Rybrevant costs and payment assistance, contact a Janssen CarePath Care Coordinator at 833-RYBREVANT (833-792-7382), Monday – Friday, 8:00 AM to 8:00 PM ET, or online.

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