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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.

LAZCLUZE™ (lazertinib)

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

Last Updated: 08/30/2024

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-lazertinib-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

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.

DOSAGE AND ADMINISTRATION IN THE PAPILLON AND MARIPOSA-2 STUDIES

The dosing regimen being evaluated 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 being evaluated 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

Cycle/Day	Daily Dose (in 250 mL IV Infusion Bag/Container)		Rate (mL/hr)
<80 kg: Q3W Dosing Regimen
Cycle 1 start daya	350 mg	Step 1b	50
Cycle 1 start daya	350 mg	Step 2	75
Cycle 1 consecutive daya	1050 mg	Step 1b	33
Cycle 1 consecutive daya	1050 mg	Step 2	50
Cycle 1 Day 8	1400 mg		65
Cycle 1 Day 15	1400 mg		85
Cycle 2 Day 1	1400 mg		125
Cycle 3 and subsequent doses	1750 mg		125
≥80 kg: Q3W Dosing Regimen
Cycle 1 start daya	350 mg	Step 1b	50
Cycle 1 start daya	350 mg	Step 2	75
Cycle 1 consecutive daya	1400 mg	Step 1b	25
Cycle 1 consecutive daya	1400 mg	Step 2	50
Cycle 1 Day 8	1750 mg		65
Cycle 1 Day 15	1750 mg		85
Cycle 2 Day 1	1750 mg		125
Cycle 3 and subsequent doses	2100 mg		125
Abbreviations: kg, kilograms; Q3W, every 3 weeks. ^aThe first dose of Cycle 1 is split to be administered over two days. Start day is the 1^st day and consecutive day is the 2^nd day. ^bOn Cycle 1 Start Day and Cycle 1 Consecutive Day, if patient tolerates the Step 1 rate, may increase to Step 2 rate after 2 hours. Administer the entire volume of the prepared dose in the IV infusion bag/container.

Required pre-infusion medications and optional pre-infusion medications for RYBREVANT in the ongoing PAPILLON and MARIPOSA-2 studies are summarized in Tables: Pre- Infusion Medications for RYBREVANT in the PAPILLON Study and Pre-Infusion Medications for RYBREVANT in the MARIPOSA-2 Study.⁷^,⁸
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.

Pre-Infusion Medications for RYBREVANT in the PAPILLON Study⁷

Cycle/Day	Medication	Dose	Route of Administration	Dosing Window Prior to RYBREVANT Administration
Required Pre-Infusion Medicationsa,b
Cycle 1 Day 1	Glucocorticoid	Dexamethasone 20 mg	IV	45-60 minutes
Cycle 1 Day 2	Glucocorticoid	Dexamethasone 10 mg or Methylprednisolone 40 mg	IV	45-60 minutes
All	Antihistamine	Diphenhydramine 25-50 mg (or equivalent)	IV	15-30 minutes
All	Antihistamine	Diphenhydramine 25-50 mg (or equivalent)	Oral	30-60 minutes
All	Antipyretic	Paracetamol (acetaminophen) 650-1000 mg (or equivalent)	IV	15-30 minutes
All	Antipyretic	Paracetamol (acetaminophen) 650-1000 mg (or equivalent)	Oral	30-60 minutes
Optional Pre-Infusion Medicationsa
Cycle 1 Day 8 and beyond	Glucocorticoidc	Dexamethasone 10 mg or Methylprednisolone 40 mg	IV	45-60 minutes
Cycle 1 Day 8 and beyond	Glucocorticoidc	Dexamethasone 10 mg or Methylprednisolone 40 mg	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: IV, intravenous; mg, milligram. ^aIf a medication noted in this table was not locally available, a similar medication and dose could be substituted and administered per local guidelines. ^bPatients for whom required medications were contraindicated could explore alternative medications with their doctor. If alternative medications were not suitable for the intent above, patients were not required to take the corresponding medication. ^cBeginning with Cycle 1 Day 8, optional pre-dose steroids could be administered prior to RYBREVANT if clinically indicated for patients who experienced an infusion-related reaction on Cycle 1 Day 1 or Cycle 1 Day 2.

Pre-Infusion Medications for RYBREVANT in the MARIPOSA-2 Study⁸

Cycle/Day	Medication	Dose	Route of Administration	Dosing Window Prior to RYBREVANT Administration
Required Pre-Infusion Medications^a,b,c
Cycle 1 Day 1	Glucocorticoid	Dexamethasone 20 mg^d	IV	60-120 minutes
Cycle 1 Day 2	Glucocorticoid	Dexamethasone 10 mg or Methylprednisolone 40 mg	IV	45-60 minutes
All	Antihistamine	Diphenhydramine 25-50 mg (or equivalent)	IV	15-120 minutes
All	Antihistamine	Diphenhydramine 25-50 mg (or equivalent)	Oral	30-150 minutes
All	Antipyretic	Paracetamol (acetaminophen) 650-1000 mg (or equivalent)	IV	15-120 minutes
All	Antipyretic	Paracetamol (acetaminophen) 650-1000 mg (or equivalent)	Oral	30-150 minutes
Optional Pre-Infusion Medications^a
Cycle 1 Day 8 and beyond	Glucocorticoid^e	Dexamethasone 10 mg or Methylprednisolone 40 mg	IV	45-60 minutes
Cycle 1 Day 8 and beyond	Glucocorticoid^e	Dexamethasone 10 mg or Methylprednisolone 40 mg	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: IV, intravenous; mg, milligram. ^aIf a medication noted in this table was not locally available, a similar medication and dose could be substituted and administered per local guidelines. ^bPatients for whom required medications were contraindicated could explore alternative medications with their doctor. If alternative medications were not suitable for the intent above, patients were not required to take the corresponding medication. ^cIf the dose of RYBREVANT is delayed until Cycle 1 Day 2 and Cycle 1 Day 3, then the dosing days of pre-infusion medications should be adjusted accordingly. ^dThis dose and recommended dosing window allow a single dose of dexamethasone to serve as the pre-infusion glucocorticoid for both chemotherapy and RYBREVANT. If chemotherapy is dosed on Cycle 1 Day 1 and RYBREVANT is dosed on Cycle 1 Day 2 and Cycle 1 Day 3, then the RYBREVANT pre-infusion glucocorticoid dose should be dexamethasone 10 mg (or methylprednisolone 40 mg) on Cycle 1 Day 2 and Cycle 1 Day 3. ^eBeginning with Cycle 1 Day 8, optional pre-dose steroids could be administered prior to RYBREVANT if clinically indicated for patients who experienced an infusion-related reaction during either day of the first dose of RYBREVANT.

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 20 August 2024.

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 2024 August 20]. 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 2024 August 20]. 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. Investigational Product Preparation and Administration Instructions for Intravenous Administration of JNJ-61186372 (Amivantamab) for Global Sites. Janssen Research & Development, LLC. TV-TEC-168067; 2024.