Initial US Approval:
2021
Key Clinical Studies:
MARIPOSA (NCT04487080); MARIPOSA-2 (NCT04988295); PAPILLON (NCT04538664); CHRYSALIS (NCT02609776)
Drug Class/Description:
Bispecific EGF receptor-directed and MET receptordirected antibody
Indications and Usage:
- in combination with lazertinib for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA approved test.
- in combination with carboplatin and pemetrexed for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, whose disease has progressed on or after treatment with an EGFR tyrosine kinase inhibitor.
- in combination with carboplatin and pemetrexed for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test.
- 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.
Dosage Administration:
The recommended dosage of RYBREVANT is based on baseline body weight and administered as an intravenous infusion after dilution.
- Administer premedications as recommended.
- Administer via a peripheral line on Week 1 and Week 2 to reduce the risk of infusion related reactions.
- Administer RYBREVANT in combination with chemotherapy weekly for 4 weeks, with the initial dose as a split infusion in Week 1 on Day 1 and Day 2, then administer every 3 weeks starting at Week 7.
- Administer RYBREVANT in combination with lazertinib or RYBREVANT as a single agent weekly for 5 weeks, with the initial dose as a split infusion in Week 1 on Day 1 and Day 2, then administer every 2 weeks starting at Week 7.
- When administering RYBREVANT in combination with lazertinib, administer anticoagulant prophylaxis to prevent venous thromboembolic (VTE) events for the first four months of treatment.
- Administer diluted RYBREVANT intravenously according to the infusion rates in Tables 8 and 9.
(Tables found in next sheet)
| Body Weight (at Baseline) | Dosage | Recommended Dose |
| RYBREVANT in Combination with Carboplatin and Pemetrexed | ||
| Less than 80 kg | Weeks 1-4 | 1,400 mg |
| Week 7 onwards | 1,750 mg | |
| Greater than or equal to 80 kg | Weeks 1-4 | 1,750 mg |
| Week 7 onwards | 2,100 mg | |
| RYBREVANT in Combination with Lazertinib or RYBREVANT as a Single Agent | ||
| Less than 80 kg | Weeks 1-5 | 1,050 mg |
| Week 7 onwards | ||
| Greater than or equal to 80 kg | Weeks 1-6 | 1,400 mg |
| Week 7 onwards | ||
Dosage Forms and Strengths:
Injection: 350 mg/7 mL (50 mg/mL) solution in a single-dose vial
Contraindications:
None.
Warnings and Precautions:
Infusion-Related Reactions (IRR): Interrupt infusion at the first sign of IRRs. Reduce the infusion rate or permanently discontinue RYBREVANT based on severity.
Interstitial Lung Disease (ILD)/Pneumonitis: Monitor for new or worsening symptoms indicative of ILD. Immediately withhold RYBREVANT in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed.
Venous Thromboembolic (VTE) Events with Concomitant Use with Lazertinib: Prophylactic anticoagulation is recommended for the first four months of treatment. Monitor for signs and symptoms of VTE and treat as medically appropriate. Withhold RYBREVANT and lazertinib based on severity. Once anticoagulant treatment has been initiated, resume RYBREVANT and lazertinib at the same dose at the discretion of the healthcare provider. Permanently discontinue RYBREVANT and continue lazertinib for recurrent VTE despite therapeutic anticoagulation.
Dermatologic Adverse Reactions: Can cause severe rash including toxic epidermal necrolysis (TEN) and acneiform dermatitis. Withhold, reduce the dose, or permanently discontinue RYBREVANT based on severity.
Ocular Toxicity: Promptly refer patients with worsening eye symptoms to an ophthalmologist. Withhold, reduce the dose, or permanently discontinue RYBREVANT based on severity.
Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception.
Adverse Reactions:
RYBREVANT in Combination with Lazertinib
- The most common adverse reactions (≥ 20%) were rash, nail toxicity, infusion-related reaction, musculoskeletal pain, stomatitis, edema, VTE, paresthesia, fatigue, diarrhea, constipation, COVID-19, hemorrhage, dry skin, decreased appetite, pruritus, nausea, and ocular toxicity.
- The most common Grade 3 or 4 laboratory abnormalities (≥ 2%) were decreased albumin, decreased sodium, increased ALT, decreased potassium, decreased hemoglobin, increased AST, increased GGT, and increased magnesium.
RYBREVANT in Combination with Carboplatin and Pemetrexed
- The most common adverse reactions (≥ 20%) were rash, nail toxicity, infusion-related reaction, fatigue, nausea, stomatitis, constipation, edema, decreased appetite, musculoskeletal pain, vomiting, and COVID-19.
- The most common Grade 3 or 4 laboratory abnormalities (≥ 2%) were decreased neutrophils, decreased leukocytes, decreased platelets, decreased hemoglobin, decreased potassium, decreased sodium, increased alanine aminotransferase, increased gamma glutamyl transferase, and decreased albumin.
RYBREVANT as a Single Agent
- The most common adverse reactions (≥ 20%) were rash, IRR, paronychia, musculoskeletal pain, dyspnea, nausea, fatigue, edema, stomatitis, cough, constipation, and vomiting.
- The most common Grade 3 or 4 laboratory abnormalities (≥ 2%) were decreased lymphocytes, decreased albumin, decreased phosphate, decreased potassium, increased alkaline phosphatase, increased glucose, increased gamma-glutamyl transferase, and decreased sodium."
Use in Specific Populations:
Lactation: Advise not to breastfeed.
Adapted from:
Every health-care provider should make their own determination regarding specific safe and appropriate patient care practices, including drug dosages and indications. The provider should always consult the most recent prescribing/product information. FDA Focus information is not guaranteed to be accurate, complete, or current. JADPRO and its editors, authors, reviewers, and commentators cannot be held responsible for any liability incurred as a consequence of the application of any of the information listed within.
