How do Exkivity and Rybrevant compare for NSCLC?
- Exkivity and Rybrevant are both targeted medications FDA-approved as second-line agents to treat locally advanced or metastatic non-small cell lung cancer (mNSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations.
- 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 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 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.
- Eligible patients have also progressed on or after platinum-based chemotherapy.
- Advanced cancer cannot be removed by surgery and metastatic cancer has spread to other parts of the body.
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.
- 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 may depend upon beneficial study results in further clinical trials.
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.
- Exkivity comes as a 40 mg capsule. It is 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. Swallow Exkivity capsules whole. Do not open, chew, or dissolve the contents of the capsules.
- Rybrevant is given as an intravenous (IV) infusion weekly for four weeks (the first dose is a split infusion over two consecutive days), then every two weeks. 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.
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.
Related: Comparing Exkivity with Rybrevant
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.
- 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.
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.
- 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?
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:
- Stomatitis (mouth sores or inflammation)
- Muscle and bone pain
- Infection of skin around nails (paronychia)
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.
Learn more: Side effects with Exkivity and Rybrevant (in more detail)
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.
- The price for Exkivity oral capsule 40 mg is around $26,335 for a supply of 120 capsules (a one month supply), depending on the pharmacy you visit. That equals about $219 per 40 mg capsule.
- The price for Rybrevant intravenous (IV) solution (350 mg/7 mL vial; 50 mg/mL) is around $3,324 for a supply of 7 milliliters. Your dose will be based on your weight. For example, for maintenance dosing starting at week 5, Rybrevant is given as an IV infusion once every 2 weeks. A 70-kg (154 lb) patient would usually receive 3 vials (1050 mg) every 2 weeks. Over a one month period, this would equal about $19,900. You will receive this medicine at a clinic or your doctor’s office and there will be additional fees associated with IV infusions and facility use.
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.
- 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. 5/2021. 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 May 5, 2022 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/
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