How do Exkivity and Rybrevant compare for NSCLC?

Note: On October 2, 2023 Takeda Pharmaceuticals announced the voluntary withdrawal of Exkivity from the U.S and global markets. Exkivity did not meet the primary endpoint of the Phase 3 EXCLAIM-2 confirmatory trial and did not meet the requirements of the Accelerated Approval granted by the FDA.

What are Exkivity and Rybrevant?

Exkivity and Rybrevant are both targeted medications used to treat locally advanced or metastatic non-small cell lung cancer (mNSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations. Exkivity treatment has been withdrawn from the U.S. market.

In clinical studies, both treatments led to responses in some patients: Close to 28% of patients had a partial response (tumor shrinkage) to Exkivity treatment and the duration of response (DoR) lasted for about 17.5 months. About 40% of participants had a response to single-agent Rybrevant treatment, with the DoR lasting for a median of 11.5 months.

Exkivity and Rybrevant both have common and serious side effects. Side effects that may occur with either treatment includes: rash, nausea, mouth sores or inflammation, nausea / vomiting, tiredness, muscle and bone pain, or an infection of skin around nails.

What are they used for?

Note: Exkivity (mobocertinib) treatment has been withdrawn from the U.S. market.

Exkivity (mobocertinib) and Rybrevant (amivantamab-vmjw) are both targeted prescription medicines used 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. Advanced cancer cannot be removed by surgery and metastatic cancer has spread to other parts of the body.

• Rybrevant is used as first-line treatment of NSCLC with EGFR exon 20 insertion mutations in combination with carboplatin and pemetrexed.
• It is also approved for use as a single agent for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy

Rybrevant from Janssen was first approved by the FDA in May 2021, and Exkivity, manufactured by Takeda Pharmaceuticals, was approved in September 2021, but withdrawn from the US market on Oct. 2, 2023.

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

• Accelerated approval is a program from the FDA that allows faster approval of certain drugs for serious conditions that have an unmet medical need.
• This allows patients to have access to promising new treatment when other options may not be available.
• Continued approval for both of these medicines and uses depended upon beneficial study results in further clinical trials.

What is NSCLC with EGFR exon 20 insertion mutations?

Non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations are a certain type of metastatic NSCLC (mNSCLS) with genetic mutations. Exon 20 mutations can allow cancers to grow and spread. Metastatic means the cancer has spread in your body away from the original site.

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?

Note: The Exkivity brand name has been discontinued in the U.S.

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 was 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 do I take Exkivity or Rybrevant?

Exkivity, before its U.S. withdrawal, was given as oral capsules taken by mouth. Rybrevant is given as an intravenous (IV) infusion.

• Exkivity came as a 40 mg capsule. It was normally given as 4 oral capsules (160 mg) once daily, with or without food. Patients should avoid eating grapefruit or drinking grapefruit juice during treatment.
• Rybrevant is given as an intravenous (IV) infusion into your vein. Premedication is recommended to reduce the risk of infusion-related reactions. Your healthcare provider will determine the correct dose for you based on your weight.

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.

Doses may need to be adjusted 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.

Take your medicine exactly as your doctor tells you to take it.

What do studies say about Exkivity and Rybrevant effectiveness?

There are no head-to-head comparative studies of Exkivity to Rybrevant, and Exkivity has now been withdrawn from the U.S market. Consult with your oncologist and cancer team to learn about which treatment option may be best for your particular situation.

Related: Comparing Exkivity with Rybrevant

Exkivity: Study 101

Approval for Exkivity, before its withdrawal from the US market, was based on 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.

• Overall, about 28% of the people (32 out of 114) had a partial response (tumor shrinkage) to Exkivity treatment and the response lasted for about 17.5 months.
• Close to 59% of patients who responded (19 out of 32) had a response that lasted at least 6 months.
• The median overall survival was 24 months (2 years). Median means that half the people lived longer than 24 months, and the other half lived less than 24 months.

On October 2, 2023 Takeda Pharmaceuticals announced the voluntary withdrawal of Exkivity from the U.S and global markets. Exkivity did not meet the primary endpoint of the Phase 3 EXCLAIM-2 confirmatory trial and did not meet the requirements of the Accelerated Approval granted by the FDA.

Related Questions

• How does Rybrevant work?
• How is Rybrevant administered?
• How effective is Exkivity (mobocertinib) for NSCLC?

Rybrevant: CHRYSALIS study

Initial 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.

• Overall, close to 40% (32 out of 81) of the evaluable participants had a response to Rybrevant treatment, with 3.7% (3 out of 81) of patients having a complete response (tumor disappear) and 36% (29 out of 81) achieving a partial response (tumor shrinkage). A complete response does not always mean that the cancer has been cured.
• The duration of response (DoR) lasted for a median of 11.5 months. About 63% of patients (20 out of 32) who responded had a response that lasted at least 6 months.
• The median overall survival was 22.8 months. Median means that half the people lived longer than 22.8 months, and the other half lived less than 22.8 months.

What are the common side effects with Exkivity and Rybrevant?

Note: The Exkivity brand name has been discontinued in the U.S. If generic versions of this product have been approved by the FDA, there may be generic equivalents available.

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 the following side effects:

• Rash
• Nausea
• Stomatitis (mouth sores or inflammation)
• Vomiting
• Tiredness (fatigue)
• Muscle and bone pain
• Infection of skin around nails (paronychia)
• Decreased appetite
• Diarrhea

In studies, Exkivity was also shown to commonly cause dry skin.

Rybrevant was also reported to commonly cause infusion-related reactions, shortness of breath, decreased edema (fluid retention, swelling), diarrhea, cough, COVID-19, and constipation.

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 carried 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. Exkivity treatment has been withdrawn from the U.S. market.

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.

Learn more: Side effects with Exkivity and Rybrevant (in more detail)

Are Exkivity or Rybrevant recommended in cancer guidelines?

Rybrevant is 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.

The Exkivity brand name has been discontinued in the U.S.

Which is more expensive, Exkivity or Rybrevant?

Before withdrawal from the U.S. market, the price for Exkivity oral capsule 40 mg was around $26,335 for a supply of 120 capsules (a one month supply), depending on the pharmacy you visit. That equaled about $219 per 40 mg capsule.

The price for Rybrevant intravenous (IV) solution (350 mg/7 mL vial; 50 mg/mL) is around $3,676 for a supply of 7 milliliters. Your dose will be based on your weight and determined by your healthcare provider.

To learn more about Rybrevant prices, discount coupons and manufacturer patient assistance programs go to The Rybrevant Price Guide.

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, but you will receive this medicine in a clinic. Speak with your healthcare provider if you questions about cost or insurance coverage.

For questions regarding Exkivity or its US withdrawal, 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 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.