SUMMARY  

• RYBREVANT (amivantamab-vmjw) is a low fucose, fully human immunoglobulin G1 (IgG1)-based bispecific antibody with immune cell-directing activity that targets epidermal growth factor receptor (EGFR) mutations and mesenchymal-epithelial transition (MET) mutations and amplifications in non-small cell lung cancer (NSCLC).¹
• LAZCLUZE (lazertinib) is a third-generation EGFR tyrosine kinase inhibitor (TKI).²
• MARIPOSA (NCT04487080) is an ongoing, phase 3, randomized study evaluating the efficacy and safety of RYBREVANT and lazertinib combination therapy (open-label, n=429) vs osimertinib (double-blind, n=429) vs lazertinib (double-blind, n=216) as first-line treatment in patients with EGFR-mutated (Exon 19 deletion [Exon19del] or Exon 21 L858R substitution), locally advanced or metastatic NSCLC.^2-4
• MARIPOSA-2 (NCT04988295) is an ongoing, phase 3, randomized, open-label study designed to assess the efficacy and safety of RYBREVANT-lazertinib-chemotherapy (pemetrexed and carboplatin; n=263) and RYBREVANT-chemotherapy (pemetrexed and carboplatin; n=131) vs chemotherapy alone (pemetrexed and carboplatin; n=263) in patients with EGFR-mutated (Exon19del or Exon 21 L858R substitution), locally advanced or metastatic NSCLC on or after osimertinib monotherapy.^5,6
• Information on prophylaxis and reactive management of oral mucositis from the MARIPOSA and MARIPOSA-2 study protocols is summarized below.
• Please refer to RYBREVANT product labeling for complete safety information, including dose modification guidelines for adverse reactions.
• Please refer to product labeling for carboplatin and/or pemetrexed for complete prescribing information.

PRODUCT LABELING

• RYBREVANT (amivantamab-vmjw) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/RYBREVANT-pi.pdf.
• LAZCLUZE (lazertinib) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/LAZCLUZE-pi.pdf.

MANAGEMENT OF ORAL MUCOSITIS IN MARIPOSA AND MARIPOSA-2 STUDIES

Mucositis is a well-recognized toxicity associated with anti-EGFR therapeutics, and may be mild/moderate and localized (grade 1-2) or severe and widespread (grade ≥3). As a result, the MARIPOSA and MARIPOSA-2 protocols include recommendations to prevent or minimize patient discomfort associated with this toxicity. Prophylaxis should occur according to local institutional practice and guidelines, and should include the following^7,8:

Prophylaxis Recommendations^7,8

• Use good oral hygiene, with dentition review and referral to an oral hygienist if necessary.
• Use a soft toothbrush.
• Use mild-flavored toothpastes.
• Use saline-peroxide or salt and soda mouthwashes 3 or 4 times per day.
• Use water soluble lubrication agents like artificial saliva (for xerostomia or dry mouth).
• Avoid spicy, acidic, hard, and hot food and beverages.

Reactive Management Guidelines^7,8

• Asymptomatic or mild symptoms: topical steroid (dexamethasone 0.5/mL elixir) and lidocaine jelly 2%-5% or solution (swish and spit) 4 times per day.
• Co-trimoxazole lozenges can be used to prevent secondary Candida infection.
• In cases of moderate to severe pain:
  • Compounded mouthwash (eg, “magic mouthwash”) including an antifungal, steroid, antihistamine, anesthetic, and/or antacid/mucosal coating agent as per local practice and guidelines.
  • Dexamethasone solution 3.3 mg/5 mL swish and spit 4 times per day, and lidocaine jelly 2%-5% or solution 4 times per day.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and DerwentDrug File (and/or other resources, including internal/external databases) was conducted on
09 June 2025. The information included in this response is limited to relevant data from the registrational studies for RYBREVANT.