Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer. If you have been diagnosed with NSCLC, your health care provider may test your cancer to see if it has certain genetic changes. Some treatments are designed to target specific genetic changes in cancer cells and are more likely to be effective tools to fight the disease when those mutations are present.
Rybrevant (amivantamab-vmjw) is a medicine that was approved by the FDA in 2021 for certain people with NSCLC. It is used for NSCLC that is locally advanced (cancer that has spread from its original location to nearby tissues, organs, or lymph nodes but has not spread to distant parts of the body) or metastatic (cancer that has spread to distant parts of the body). Rybrevant is for people whose NSCLC has certain genetic changes, including: an epidermal growth factor receptor (EGFR) exon 19 deletion mutation, an exon 21 L858R substitution mutation, or an EGFR exon 20 insertion mutation. If you do not have one of these mutations, Rybrevant will not work well for your NSCLC. Before starting Rybrevant, your health care provider will take a blood or tissue sample and send it for testing to make sure that you have one of these mutations.
How Does Rybrevant Work for NSCLC?
Rybrevant is a special type of medicine called a bispecific antibody, which means it is designed to attach to two different targets on cancer cells. Rybrevant specifically attaches to two proteins called EGFR and MET. These proteins help cancer cells grow and spread.
By attaching to both EGFR and MET, Rybrevant blocks the signals that tell cancer cells to grow. It can also cause these proteins to break down, making it harder for the cancer cells to survive.
In addition to blocking these growth signals, Rybrevant helps the body’s immune system recognize and attack the cancer cells. It acts like a “tag” that marks the cancer cells, so immune cells can destroy them.
How Do I Use Rybrevant?
Rybrevant is given as an infusion into your vein (IV). Your first dose will be split up and given over two days. After that, you will get an infusion weekly for several weeks, and then it will be spaced out further, so that you get your dose of Rybrevant every two to three weeks.
The decision to use Rybrevant by itself or with other medicines for cancer will depend on which genetic mutations you have and what medicines you have used before for your NSCLC. The dose that you will be given will depend on whether or not it is given with other medicines (and if it is, which medicines it is given with) and how much you weigh.
The Rybrevant infusion can cause side effects like difficulty breathing, fever, chills, nausea and vomiting, and flushing (skin redness and warmth in the face, neck, or chest) — also called infusion-related reactions. Before you get your infusion, you will be given medicines by mouth or through your IV line to help lower your risk of these side effects and make them less severe if they happen.
What Serious Side Effects Can Happen and How Will They Affect My Treatment?
Some of the potentially serious side effects that can happen in people using Rybrevant include infusion-related reactions, lung inflammation (also called interstitial lung disease or pneumonitis), blood clots when used in combination with lazertinib (also called venous thromboembolism), eye problems, and skin reactions. If any of these side effects happen while you are using Rybrevant, your health care provider may lower your dose or temporarily or permanently stop Rybrevant. You may also be given additional medicines to help with these side effects if they happen.
If you are taking Rybrevant in combination with another medicine for NSCLC called lazertinib (Lazcluze), your health care provider may prescribe an anticoagulant (“blood thinner”) medicine for at least a few months to lower your risk of having blood clots.Your health care provider may also prescribe a cream for your skin to help prevent skin reactions while taking both of these medicines.
How Was Rybrevant Studied for NSCLC?
Several different clinical trials were done to study the effects of Rybrevant in people with locally advanced or metastatic NSCLC who had different characteristics. Key details from the main studies that were done are described below.
MARIPOSA study
People in this study had not received any previous treatment for their NSCLC and had either EGFR exon 19 deletions or exon 21 L858R substitution. Half (429) of the people got Rybrevant and lazertinib, and the other 429 people got osimertinib (Tagrisso).
MARIPOSA-2 study
People in this study had worsening NSCLC during or after taking osimertinib and had either EGFR exon 19 deletions or exon 21 L858R substitution. One group of 263 people got carboplatin and pemetrexed (chemotherapy), and another group of 131 people got Rybrevant, carboplatin, and pemetrexed (chemotherapy plus Rybrevant).
PAPILLON study
People in this study had not received any previous treatment for their NSCLC and had an EGFR exon 20 insertion mutation. One group of 155 people got carboplatin and pemetrexed (chemotherapy), and another group of 153 people got Rybrevant, carboplatin, and pemetrexed (chemotherapy plus Rybrevant).
CHRYSALIS study
People in this study had worsening cancer during or after previous chemotherapy for their NSCLC and had an EGFR exon 20 insertion mutation. All 81 people got Rybrevant.
What Were the Study Populations in Each Study?
MARIPOSA
- Median (middle) age of 63
- 61% female
- Race/ethnicity
- 58% Asian, 38% White, 1.6% American Indian or Alaska Native, 0.8% Black or African American, 0.2% Native Hawaiian or other Pacific Islander, 0.6% unknown race or multiple races
- 12% Hispanic or Latino
- 69% never smoked before
- 89% had stage 4 NSCLC
MARIPOSA-2
- Median (middle) age of 62
- 60% female
- Race/ethnicity
- 48% Asian, 46% White, 1% American Indian or Alaska Native, 1% Black or African American, 0.5% multiple races, 2.8% with unknown or unreported race
- 8% Hispanic or Latino
- 65% never smoked before
- 99.7% had stage 4 NSCLC
PAPILLON
- Median (middle) age of 62
- 58% female
- Race/ethnicity
- 61% Asian, 36% White, 0.7% Black or African American, 2.3% with unreported race
- 7% Hispanic or Latino
- 58% never smoked before
- 84% had stage 4 NSCLC
CHRYSALIS
- Median (middle) age of 62
- 59% female
- Race
- 49% Asian, 37% White, 2.5% Black, 11% with unreported race
- 53% never smoked before
- All had metastatic NSCLC
What Were the Main Outcomes?
The main outcome of the MARIPOSA, MARIPOSA-2, and PAPILLON studies was progression-free survival, which is the amount of time people live with their cancer before it gets worse after starting a certain medicine. This outcome was also looked at in the CHRYSALIS study.
What Benefits Were Seen With Rybrevant?
Key results from each of the studies are described below. Your results may differ from what was seen in clinical studies.
MARIPOSA
Most people who got osimertinib had progression-free survival between 14.8 and 18.5 months. In contrast, most people who got Rybrevant and lazertinib had progression-free survival between 19.1 and 27.7 months.
This study also looked at overall survival. Two years after people started this study, 69% of people who got osimertinib and 74% of people who got Rybrevant and lazertinib were alive.
MARIPOSA-2
Most people who got chemotherapy had progression-free survival between 4 and 4.4 months. In contrast, most people who got Rybrevant with chemotherapy had progression-free survival between 5.6 and 8.4 months.
PAPILLON
Most people who got chemotherapy had progression-free survival between 5.6 and 7.3 months. In contrast, most people who got Rybrevant with chemotherapy had progression-free survival between 9.8 and 13.7 months.
CHRYSALIS
Unlike the other studies, the main outcome that was looked at in this study was the overall response rate. The overall response rate measures how many people had a partial or complete response.
- Partial response: a decrease in the amount of cancer in your body
- Complete response: no signs of cancer in your body
In this study, 40% of people who got Rybrevant had an overall response. Of these, 4% had a complete response and 36% had a partial response.
Most people who got Rybrevant had progression-free survival between 6.5 and 10.9 months.
Is There Any Cost Assistance Available?
There is a patient support program offered by the drugmaker that may help you afford Rybrevant. Your health care provider can help you get started. You can find out more at rybrevant.com/savings-support or by calling 833-565-9631.
