Rybrevant

About Amivantamab

• The FDA granted accelerated approval to Amivantamab (Rybrevant) on May 21, 2021, for treating adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion mutations. 
• This decision was based on findings from the CHRYSALIS trial (NCT02609776), a multicenter, non-randomized, open-label study involving individuals with advanced NSCLC possessing EGFR exon 20 insertion mutations. Results from the trial showcased an overall response rate (ORR) of 40%, with a median response duration of 11.1 months.
• Amivantamab, marketed as Rybrevant, is a bispecific monoclonal antibody used in the treatment of non-small cell lung cancer (NSCLC). This medication marks a significant milestone as the first treatment designed specifically for adults with NSCLC carrying EGFR exon 20 insertion mutations. Amivantamab Janssen, represents a promising advancement in the field of oncology, providing hope for patients with this challenging form of lung cancer.
• Amivantamab works through a dual mechanism of action by targeting two crucial receptors in cancer progression: the epidermal growth factor receptor (EGFR) and the mesenchymal–epithelial transition (MET) receptor. By simultaneously binding to these receptors, it disrupts signaling pathways that support tumor growth and survival. This approach enhances the inhibition of cancer cell proliferation and survival, making it a promising treatment for non-small cell lung cancer (NSCLC) with specific genetic mutations, including EGFR exon 20 insertion mutations.

Strength: 

Rybrevant injection of 350 mg/7 mL (50 mg/mL) solution in a single-dose vial. 

Recommended Dosage:

Prepare Rybrevant for intravenous infusion by ensuring the solution’s color and absence of particulate matter. Determine the dosage based on the patient’s weight, withdraw the required volume from the vials, and add it to a 250 mL infusion bag with appropriate diluent. Administer the solution within 10 hours at room temperature using an infusion set with a flow regulator and sterile filter. 

Avoid concurrent infusion with other agents and initiate peripheral line administration for the first two weeks. Prepare the medicine close to administration time during the initial infusion and follow recommended infusion rates.

The recommended dosage of Amivantamab is based on the patient’s baseline body weight:

• If the patient weighs less than 80 kg, the initial dose is 1050 mg per week for four weeks, followed by 1050 mg every 2 weeks.
• For patients weighing 80 kg or more, the initial dose is 1400 mg per week for four weeks, followed by 1400 mg every 2 weeks.

The first dose should be split between Day 1 and Day 2 of Week 1, with subsequent doses given as a single infusion. Patients should receive premedications such as an antihistamine and antipyretic before each infusion. Additionally, a glucocorticoid is required only for the first two doses of Week 1 and as needed for subsequent infusions.

Important:

Prior to initiating treatment, it is essential to notify your healthcare provider if you are pregnant, planning to conceive, or breastfeeding. Additionally, disclose any pre-existing medical conditions and provide details of all current medications, including prescriptions, over-the-counter drugs, vitamins, and herbal supplements. This information enables your healthcare provider to assess potential interactions and customize your treatment plan accordingly.

Warnings & Precautions

• In infusion-Related Reactions (IRRs), immediate interruption of infusion upon suspicion of IRRs is essential, with subsequent reduction or permanent discontinuation of Rybrevant based on severity. 
• Premedication with antihistamines, antipyretics, and glucocorticoids is recommended, and administration via a peripheral line for the first two weeks is advised to monitor and manage potential infusion reactions. 
• Monitoring for signs of interstitial lung disease (ILD)/pneumonitis is crucial, with immediate withholding and permanent discontinuation if confirmed. 
• Patients should be monitored for dermatologic adverse reactions, such as rash, pruritus, and dry skin, with appropriate sun protection measures and prompt dermatologist referral for severe reactions. 
• Ocular symptoms warrant prompt ophthalmologist referral and caution regarding embryo-fetal toxicity necessitates informing females of reproductive potential about contraception use.

Common Rybrevant Side Effects:

• Rash
• Infusion-related reactions (IRR)
• Paronychia
• Musculoskeletal pain
• Dyspnea
• Nausea
• Fatigue
• Edema
• Stomatitis
• Cough
• Constipation
• Vomiting

Grade 3 or 4 laboratory abnormalities (≥ 2%)

• Decreased lymphocytes
• Decreased albumin
• Decreased phosphate
• Decreased potassium
• Increased alkaline phosphatase
• Increased glucose
• Increased gamma-glutamyl transferase
• Decreased sodium

Use in Specific Population

• Rybrevant presents potential risks of fetal harm if administered to pregnant women due to its mechanism of action and findings in animal models. 
• There is currently insufficient data on its use in pregnant women or animal studies to evaluate these risks accurately. 
• Additionally, there is no information available regarding the presence of amivantamab-vmjw in human milk, its impact on milk production, or its effects on breastfed infants. 
• Therefore, it is advised that women avoid breastfeeding while undergoing treatment with Rybrevant and for a period of 3 months after the final dose to prevent serious adverse reactions in breastfed infants. 
• Prior to initiating Rybrevant treatment, pregnancy testing should be conducted for females of reproductive potential, and effective contraception is recommended throughout the treatment duration and for 3 months following the final dose. 
• The safety and efficacy of Rybrevant have not been established in pediatric patients, and there were no significant differences in safety or efficacy observed between older and younger patients.

Storage and Handling

• Keep Rybrevant stored in its original carton in a refrigerator at a temperature between 2°C to 8°C (36°F to 46°F) to shield it from light exposure. Avoid freezing the medication.
• Do not freeze the medicine. 
• Keep the medicine away from pets and children.