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RYBREVANT®

(amivantamab-vmjw)

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This information is intended for US healthcare professionals to access current scientific information about J&J Innovative Medicine products. It is prepared by Medical Information and is not intended for promotional purposes, nor to provide medical advice.

RYBREVANT® (amivantamab-vmjw)

Medical Information

RYBREVANT - Dosage and Administration - Combination with Carboplatin and Pemetrexed (PAPILLON and MARIPOSA-2 Studies)

Last Updated: 09/05/2025

SUMMARY

  • The company cannot recommend any practices, procedures or usage that deviate from the approved labeling.
  • 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
  • PAPILLON (NCT04538664) is an ongoing, phase 3, randomized, open-label study designed to compare the efficacy and safety of RYBREVANT plus chemotherapy (carboplatin and pemetrexed) vs chemotherapy alone (carboplatin and pemetrexed) in patients with untreated locally advanced or metastatic NSCLC and EGFR Exon 20 insertion (Exon20ins) mutations.3,4
  • MARIPOSA-2 (NCT04988295) is an ongoing, phase 3, open-label, randomized study designed to assess the efficacy and safety of RYBREVANT-LAZCLUZE-chemotherapy (carboplatin and pemetrexed) and RYBREVANT-chemotherapy (carboplatin and pemetrexed) vs chemotherapy alone (carboplatin and pemetrexed) in patients with EGFR-mutated (Exon 19 deletion [Exon19del] or Exon 21 L858R substitution) locally advanced or metastatic NSCLC on or after osimertinib monotherapy.5,6

PRODUCT LABELING

DOSAGE AND ADMINISTRATION IN THE PAPILLON AND MARIPOSA-2 STUDIES

The dosing regimen for RYBREVANT in combination with chemotherapy (carboplatin and pemetrexed) in the ongoing phase 3 PAPILLON and MARIPOSA-2 studies is described below. Please refer to the approved labeling for the individual chemotherapy drugs for additional information regarding dosage and administration.

  • Study treatment was administered in the following order7,8:
    • On Day 1 of each cycle, pemetrexed was the first administered treatment.
    • On Day 1 of Cycles 1-4, carboplatin was administered after pemetrexed (and before RYBREVANT).
    • RYBREVANT was administered after all chemotherapy treatment.
  • The dosing regimen for RYBREVANT in combination with carboplatin and pemetrexed is as follows7,8:
    • Pemetrexed 500 mg/m2 on Day 1 of each 21-day cycle.
    • Carboplatin AUC 5 on Day 1 of each 21-day cycle, for up to 4 cycles.
    • RYBREVANT 1400 mg (1750 mg if body weight is ≥80 kg) by intravenous (IV) infusion on Cycle 1 Days 1/2, 8, and 15, and Cycle 2 Day 1, then 1750 mg (2100 mg if body weight ≥80 kg) on Day 1 of each 21-day cycle, starting with Cycle 3 (Table: Infusion Rates for RYBREVANT Administration Every 3 Weeks).

Infusion Rates for RYBREVANT Administration Every 3 Weeks9
Body Weight <80 kg
Week
Dose
(per 250 mL Bag)
Initial Infusion Rate
(mL/hr)
Subsequent Infusion Ratea
(mL/hr)
Week 1 (split dose infusion)
   Week 1 Day 1
350 mg
50
75
   Week 1 Day 2
1050 mg
33
50
Week 2
1400 mg
65
Week 3
1400 mg
85
Week 4
1400 mg
125
Week 7 and Q3W thereafter
1750 mg
125
Body Weight ≥80 kg
Week
Dose
(per 250 mL Bag)
Initial Infusion Rate
(mL/hr)
Subsequent Infusion Ratea
(mL/hr)
Week 1 (split dose infusion)
   Week 1 Day 1
350 mg
50
75
   Week 1 Day 2
1400 mg
25
50
Week 2
1750 mg
65
Week 3
1750 mg
85
Week 4
1750 mg
125
Week 7 and Q3W thereafter
2100 mg
125
Abbreviation: IRR, infusion-related reaction.
aIn the absence of IRRs, increase the initial infusion rate to the subsequent infusion rate after 2 hours.

Pre-infusion Medications

  • Recommended pre-infusion medications for RYBREVANT are summarized in the Table: Premedications.9
    • Two days before the first infusion:
      • Oral dexamethasone - During the 2 days prior to the initial RYBREVANT infusion, patients should receive dexamethasone 8 mg orally, twice daily. On the day of the initial infusion (Week 1, Day 1), patients should receive dexamethasone 8 mg orally, 1 hour prior to infusion in addition to IV dexamethasone to further reduce the risk of infusion-related reaction (IRR).
    • Day of infusion:
      • Prior to initial infusion of RYBREVANT (Week 1, Days 1 and 2), administer antihistamines, antipyretics, and glucocorticoids to reduce the risk of IRRs. For subsequent doses, administer antihistamines and antipyretics. Administer antiemetics as needed.

Premedications9
Medication
Dose
Route of Administration
Dosing Window Prior to RYBREVANT
Administration
Antihistaminea
Diphenhydramine (25-50 mg) or equivalent
IV
15-30 minutes
Oral
30-60 minutes
Antipyretica
Paracetamol/acetaminophen
(650-1000 mg)
or equivalent
IV
15-30 minutes
Oral
30-60 minutes
Glucocorticoidb
Dexamethasone (20 mg)
or equivalent
IV
60-120 minutes
Glucocorticoidc
Dexamethasone (10 mg)
or equivalent
IV
45-60 minutes
aRequired at all doses.
bRequired at initial dose (Week 1, Day 1).
cRequired at second dose (Week 1, Day 2); optional for subsequent doses.

Optional Pre-Infusion Medications for RYBREVANT in the PAPILLON Study7
Cycle/Day
Medication
Dose
Route of Administration
Dosing Window Prior to RYBREVANT
Administration
Cycle 1 Day 8 and beyond
Glucocorticoidb
Dexamethasone 10 mg or Methylprednisolone 40 mg
IV
45-60 minutes
Oral
60-90 minutes
Any
Histamine H2- antagonist
Ranitidine 50 mg (or equivalent)
IV
15-30 minutes
Any
Antiemetic
Ondansetron 8-16 mg (or equivalent)
Oral or IV
15-30 minutes
Abbreviations: IRR, infusion-related reaction; IV, intravenous.
aIf a medication noted in this table was not locally available, a similar medication and dose could be substituted and administered per local guidelines.
bBeginning with Cycle 1 Day 8, optional pre-dose steroids could be administered prior to RYBREVANT if clinically indicated for patients who experienced an IRR on Cycle 1 Day 1 or Cycle 1 Day 2.

Optional Pre-Infusion Medications for RYBREVANT in the MARIPOSA-2 Study8
Cycle/Day
Medication
Dose
Route of Administration
Dosing Window Prior to RYBREVANT Administration
Cycle 1 Day 8 and beyond
Glucocorticoidb
Dexamethasone 10 mg or Methylprednisolone 40 mg
IV
45-60 minutes
Oral
60-90 minutes
Any
Histamine H2-antagonist
Ranitidine 50 mg (or equivalent)
IV
15-30 minutes
Any
Antiemetic
Ondansetron 8-16 mg (or equivalent)
Oral or IV
15-120 minutes
Abbreviations: IRR, infusion-related reaction; IV, intravenous.
aIf a medication noted in this table was not locally available, a similar medication and dose could be substituted and administered per local guidelines.
bBeginning with Cycle 1 Day 8, optional pre-dose steroids could be administered prior to RYBREVANT if clinically indicated for patients who experienced an IRR during either day of the first dose of RYBREVANT.
  • Patients may receive other pre-treatment or concomitant treatment for carboplatin or pemetrexed as recommended by approved labeling, local practice guidelines, or as clinically indicated. Permitted prophylactic medications may include the following7,8:
    • Appropriate prophylactic antiemetic regimens for emesis associated with carboplatin, in accordance with institutional practice or national oncology supportive care guidelines.
    • Granulocyte-colony stimulating factors (G-CSFs) could not be used prophylactically during screening. Use of prophylactic colony stimulating factors could be considered after first dose as per local guidelines or approved labeling.

Literature Search

A literature search of MEDLINE®, Embase®, BIOSIS Previews®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 14 August 2025.

References

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1 Moores SL, Chiu ML, Bushey BS, et al. A novel bispecific antibody targeting EGFR and cMet is effective against EGFR inhibitor-resistant lung tumors. Cancer Res. 2016;76(13):3942-3953.  
2 Cho BC, Felip E, Hayashi H, et al. MARIPOSA: phase 3 study of first-line amivantamab + lazertinib versus osimertinib in EGFR-mutant non-small cell lung cancer. Future Oncol. 2022;18(6):639-647.  
3 Janssen Research & Development, LLC. A randomized, open-label phase 3 study of combination amivantamab and carboplatin-pemetrexed therapy, compared with carboplatin-pemetrexed, in patients with EGFR exon 20ins mutated locally advanced or metastatic non-small cell lung cancer. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 August 14]. Available from: https://clinicaltrials.gov/study/NCT04538664 NLM Identifier: NCT04538664.  
4 Zhou C, Tang KJ, Cho BC, et al. Amivantamab plus chemotherapy in NSCLC with EGFR exon 20 insertions. N Engl J Med. 2023;389(22):2039-2051.  
5 Janssen Research & Development, LLC. A phase 3, open-label, randomized study of amivantamab and lazertinib in combination with platinum-based chemotherapy compared with platinum-based chemotherapy in patients with EGFR-mutated locally advanced or metastatic non-small cell lung cancer after osimertinib failure. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 August 14]. Available from: https://clinicaltrials.gov/study/NCT04988295 NLM Identifier: NCT04988295.  
6 Passaro A, Wang J, Wang Y, et al. Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. Ann Oncol. 2024;35(1):77-90.  
7 Zhou C, Tang KJ, Cho BC, et al. Clinical Protocol for: Amivantamab plus chemotherapy in NSCLC with EGFR exon 20 insertions. N Engl J Med. 2023;389(22):2039-2051.  
8 Passaro A, Wang J, Wang Y, et al. Clinical Protocol for: Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. Ann Oncol. 2024;35(1):77-90.  
9 Data on File. Amivantamab Intravenous Formulation Company Core Data Sheet. Janssen Research & Development, LLC. EDMS-ERI-206387231; 2025.