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 mutations. On October 2, 2023, Exkivity treatment was withdrawn from the U.S. market.
- In clinical studies, both treatments led to responses in some patients with Exon 20 mutations: 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.
- Rybrevant plus orally-administered Lazcluze (lazertinib) is also approved for treatment of adults with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations.
Exkivity and Rybrevant both have common and serious side effects. Side effects that may occur with either treatment include: rash, nausea, mouth sores or inflammation, nausea / vomiting, tiredness, dry skin, 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Note: Exkivity (mobocertinib) treatment has been withdrawn from the U.S. market.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 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.
- Intravenous (IV) 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 adults 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.
- In August 2024 Rybrevant plus orally-administered Lazcluze (lazertinib) was approved as first-line treatment of adults with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test.
- In Sept. 2024 it was approved in combination with carboplatin and pemetrexed as a second-line treatment for NSCLC in patients whose disease has worsened on or after treatment with an EGFR tyrosine kinase inhibitor (TKI).
Rybrevant is from Janssen Pharmaceuticals and was first approved by the FDA in May 2021. Exkivity, manufactured by Takeda Pharmaceuticals, was approved in September 2021, but withdrawn from the US market on Oct. 2, 2023.
What is NSCLC with EGFR exon mutations?
A gene that makes a protein that is involved in cell growth and cell survival. EGFR is a protein found on cells that helps them grow, but an EGFR gene mutation (or gene change) can cause cells to grow out of control, which can cause cancer.
Changed forms of the EGFR gene and protein have been found in some types of cancer, including NSCLC. A doctor looks for this biomarker, called an EGFR mutation, in people diagnosed with non-small cell lung cancer (NSCLC), using a special approved test to help plan for drug treatment.
Exon 20 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 of 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%.
EGFR exon 19 deletions or exon 21 L858R substitutions
EGFR exon 19 deletions (which means a piece of genetic material is missing) and exon 21 L858R substitutions (which means genetic material is incorrectly arranged) are the most common mutations found in NSCLC, accounting for about 90% of mutations.
NSCLC patients with exon 19 deletions and exon 21 L858R substitutions have longer progression-free survival (PFS) when treated with TKIs compared with traditional chemotherapy
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. Rybrevant also targets EGFR exon 19 deletions or exon 21 L858R substitution 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 options 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 and MARIPOSA studies
EGFR exon 20 insertion mutations
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. 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.
EGFR exon 19 deletions or substitution mutations
The Phase 3 MARIPOSA study enrolled 1,074 patients to evaluate Rybrevant in combination with Lazcluze compared to osimertinib (Tagrisso) used alone and Lazcluze used alone (an unapproved treatment for NSCLC) in 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.
Secondary endpoints including overall survival (OS), overall response rate (ORR), duration of response (DOR), second progression-free survival (PFS2) and intracranial PFS.
- MARIPOSA 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
In the Phase 3 MARIPOSA-2 study 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 (brand name: Tagrisso).
Researchers found statistically significant progression-free survival (PFS) benefits, the primary endpoint, in this study. PFS is the length of time during and after treatment that a patient lives with the cancer but it does not get worse.
- 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 not a significant difference seen in the overall survival (OS) between the 2 groups when evaluated at the pre-specified time point, but the numbers were similar.
- Overall survival (OS) is the length of time from the start of treatment that a patient is still alive.
- The median OS was 17.7 months in the Rybrevant + chemotherapy group and 15.3 months in the group that received only chemotherapy.
Note: The disappearance of all signs of cancer in response to treatment (a complete response) does not always mean the cancer has been cured.
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
- Dry skin
Rybrevant was also reported to commonly cause infusion-related reactions, shortness of breath, decreased edema (fluid retention, swelling), blood clots in the veins, paresthesia (tingling feeling in skin), itching, bleeding, diarrhea, cough, COVID-19, ocular (eye) toxicity 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.
Rybrevant used with lazertinib can cause serious and possibly deadly venous thromboembolic
(VTEs) events, including deep vein thrombosis and pulmonary embolism. These are blood clots in your veins or lungs. The majority of these events occurred during the first 4 months of therapy.
- When Rybrevant is given in combination with lazertinib, your doctor will administer anticoagulant prophylaxis (blood thinners) to prevent the formation of blood clots for the first four months of treatment.
Learn more: Side effects with Exkivity and Rybrevant (in more detail)
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.
References
- Rybrevant (amivantamab-vmjw) Plus Standard of Care Approved in the U.S. as First and Only Targeted Regimen to Cut Risk of Disease Progression by More Than Half in Second-Line EGFR-Mutated Advanced Lung Cancer. Sept 19, 2024. Drugs.com. Accessed Nov 10, 2024 at https://www.drugs.com/newdrugs/rybrevant-amivantamab-vmjw-plus-standard-care-approved-u-s-first-only-targeted-regimen-cut-risk-6377.html
- FDA approves lazertinib with amivantamab-vmjw for non-small lung cancer. US Food and Drug Administration (FDA). 8/20/2024. Accessed Aug 22, 2024 at https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lazertinib-amivantamab-vmjw-non-small-lung-cancer
- Takeda Provides Update on Voluntary Withdrawal Exkivity (mobocertinib). Drugs.com. October 2, 2023. Accessed Oct 31, 2023 at https://www.drugs.com/clinical_trials/takeda-provides-update-voluntary-exkivity-mobocertinib-21074.html
- Park K, Haura EB, Leighl NB, et al. Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study. J Clin Oncol. 2021 Oct 20;39(30):3391-3402. doi: 10.1200/JCO.21.00662.
- Zhou C, Ramalingam SS, Kim TM, et al. Treatment Outcomes and Safety of Mobocertinib in Platinum-Pretreated Patients With EGFR Exon 20 Insertion-Positive Metastatic Non-Small Cell Lung Cancer: A Phase 1/2 Open-label Nonrandomized Clinical Trial [published correction appears in JAMA Oncol. 2022 Feb 24;:]. JAMA Oncol. 2021;7(12):e214761. doi:10.1001/jamaoncol.2021.4761
- Rybrevant (amivantamab-vmjw) prescribing information. 3/2024. Janssen Biotech, Inc, Horsham, PA. Accessed May 5, 2022 at https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/RYBREVANT-pi.pdf
- Exkivity (mobocertinib) prescribing information. 9/2021. Takeda Pharmaceuticals America, Inc.
Lexington, MA. Accessed March 5, 2024 at https://content.takeda.com/?contenttype=pi&product=exkivity&language=eng&country=usa&documentnumber=1 - NCCN Guidelines. Non-small cell lung cancer. Version 3.2022. Accessed May 5, 2022 at https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf
- Leal JL, Alexander M, Itchins M, et al. EGFR Exon 20 Insertion Mutations: Clinicopathological Characteristics and Treatment Outcomes in Advanced Non-Small Cell Lung Cancer. Clin Lung Cancer. 2021 Nov;22(6):e859-e869. doi: 10.1016/j.cllc.2021.04.009.
- New Amivantamab Data from CHRYSALIS Study Show Robust Clinical Activity and Durable Responses in Patients with Metastatic or Unresectable Non-Small Cell Lung Cancer and EGFR Exon 20 Insertion Mutations. Jan. 28, 2021. J&J. Innovation. Accessed May 5, 2022 at https://www.jnj.com/new-amivantamab-data-from-chrysalis-study-show-robust-clinical-activity-and-durable-responses-in-patients-with-metastatic-or-unresectable-non-small-cell-lung-cancer-and-egfr-exon-20-insertion-mutations
- Rybrevant.com. Study results. Janssen Biotech, Inc, Horsham, PA. Accessed May 5, 2022 https://www.rybrevanthcp.com/study-results
- Exkivity. Dosing and Patient Management Guide. Takeda Pharmaceuticals America, Inc. Lexington, MA. Accessed May 5, 2022 at https://www.exkivityhcp.com/files/EXKIVITY-Dosing-and-Patient-Management-Guide.pdf
- Takeda Oncology. Is there a way to change course for EGFR exon 20 insertion+ mNSCLC patients? Takeda Pharmaceuticals America, Inc.
Lexington, MA. Accessed May 5, 2022 at https://www.changecourseforexon20.com/ - https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/symptoms-diagnosis/biomarker-testing/egfr#
Read next
Is small cell or non-small cell lung cancer worse?
Generally, small cell lung cancer (SCLC) is worse than non-small cell lung cancer (NSCLC). SCLC accounts for about 10-15% of people who have lung cancer and is the most aggressive form of lung cancer. SCLC usually starts in the breathing tubes (bronchi), and although the cells are small, they grow very quickly and create large tumors. Early on in the course of the disease, there are rarely any symptoms. If caught early (limited-stage disease) 20-25% of people can be potentially cured. Extensive SCLC is more difficult to treat. Continue reading
Is non-small cell lung cancer hereditary?
A hereditary family history of lung cancer is one of the many risk factors for developing non-small cell lung cancer. About 8% of lung cancers are thought to be inherited or linked to gene changes, but smoking and air pollution remain the primary causes of lung cancer. Continue reading
How aggressive is non-small cell lung cancer?
Non-small cell lung cancer (NSCLC) tends to spread more slowly than small cell lung cancer (SCLC). About 80% of all lung cancers are diagnosed as NSCLC. Some forms of NSCLC do grow rapidly, such as large cell undifferentiated carcinoma and large cell neuroendocrine carcinoma. Lung cancer most commonly spreads to the liver, brain, bones or adrenal glands. Continue reading
Related medical questions
- Does smoking cause non-small cell lung cancer?
- What type of lung cancer is Vizimpro used to treat?
- What type of cancer is Tecentriq used to treat?
- How long does it take for Keytruda to work?
- Why give Taxol (Paxel) before carboplatin?
- What is the difference between Opdivo and Keytruda?
- Pembrolizumab vs. nivolumab: How do they compare?
- What is Paxel called in the USA?
- How effective is Lumakras, what's the survival rate?
- What is the difference between Mvasi and Avastin?
- How effective is Tabrecta?
- Are there cost-saving programs for Tecentriq?
- How does erlotinib work (mechanism of action)?
- How long can I take Gilotrif (afatinib) for?
- Will Tabrecta cure lung cancer?
- How effective is atezolizumab (Tecentriq)?
- Is atezolizumab (Tecentriq) a chemotherapy or immunotherapy drug?
- How does Retevmo work?
- Is Tabrecta a chemotherapy drug?
- Is Gilotrif (afatinib) a chemotherapy drug?
- How long do you take Alecensa for?
- How effective is Alecensa for ALK-positive NSCLC?
- What is the mechanism of action for Alecensa (alectinib)?
- Can Tarceva (erlotinib) cure lung cancer?
- How does pemetrexed work?
- How does Gilotrif (afatinib) work?
- Does atezolizumab (Tecentriq) cause hair loss?
- How long does it take for Xalkori to work?
- How to pronounce Xalkori?
- How does Alecensa work?
Drug information
Related support groups
- Rybrevant (3 questions, 3 members)
- Exkivity (2 questions, 3 members)
- Non-Small Cell Lung Cancer (52 questions, 70 members)