For APPs & Nurses

Primary Endpoint

For previously treated adult patients with locally advanced or metastatic EGFR+ NSCLC

RYBREVANT® + chemotherapy—the first & only targeted combination to significantly improve PFS post-osimertinib1,2

RYBREVANT® + chemotherapy (carboplatin/pemetrexed) reduced the risk of progression or death by 52%1,3

Rybrevant + chemotherapyRybrevant + chemotherapy Mobile
RYBREVANT® + chemotherapy demonstrated a median PFS of 6.3 months (95% CI: 5.6, 8.4) vs 4.2 months (95% CI: 4, 4.4) for chemotherapy alone3
  • At 6 months: 51% of patients were progression-free with RYBREVANT® + chemotherapy vs 30% of patients with chemotherapy alone3
  • At 12 months: 22% of patients were progression-free with RYBREVANT® + chemotherapy vs 13% of patients with chemotherapy alone3
MARIPOSA-2 study design

NCCN Category 1 (preferred) after osimertinib4

Amivantamab-vmjw (RYBREVANT®) + chemotherapy* is the ONLY NCCN Category 1 (preferred) treatment option for patients with EGFR+† nonsquamous metastatic NSCLC progressing on osimertinib who are symptomatic with multiple systemic lesions.

*Chemotherapy is carboplatin and pemetrexed.
†EGFR exon 19 deletion or exon 21 L858R mutations.

PFS across patient subgroups3

SubgroupAnalysisImgSubgroupAnalysisImg

CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; ex19del, exon 19 deletion; HR, hazard ratio; mNSCLC, metastatic non–small cell lung cancer; NCCN, National Comprehensive Cancer Network; NSCLC, non–small cell lung cancer; PFS, progression-free survival.

Secondary Endpoints

For previously treated adult patients with locally advanced or metastatic EGFR+ NSCLC

RYBREVANT® + chemotherapy demonstrated significantly higher response rates compared to chemotherapy alone1

Overall response rates1,5

improvement in intracranial PFS in the ITT populationimprovement in intracranial PFS in the ITT population Mobile

~2X ORR with RYBREVANT® + chemotherapy compared to chemotherapy alone

Duration of response1,5

improvement in intracranial PFS in the ITT populationimprovement in intracranial PFS in the ITT population Mobile

32% of patients with RYBREVANT® + chemotherapy had a response of more than 6 months and 20% with chemotherapy alone5

This was a prespecified analysis and was not powered to show statistical significance.

For previously treated adult patients with locally advanced or metastatic EGFR+ NSCLC

Interim OS results1,6

At the prespecified second interim analysis of OS, with 85% of the deaths needed for the final analysis, there was no statistically significant difference in OS. The median OS was 17.7 months (95% CI: 16, 22.4) in the RYBREVANT® + chemotherapy arm and 15.3 months (95% CI: 13.7, 16.8) in the chemotherapy arm, with an HR of 0.73 (95% CI: 0.54, 0.99). Final OS analysis has not yet been formally tested.

For previously treated adult patients with locally advanced or metastatic EGFR+ NSCLC

Intracranial PFS3*

RYBREVANT® + chemotherapy median icPFS was 12.5 months (95% CI: 10.8, NE) and 8.3 months (95% CI: 7.3, 11.3) with chemotherapy alone3

improvement in intracranial PFS in the ITT populationimprovement in intracranial PFS in the ITT population Mobile

This was a prespecified analysis and was not powered to show statistical significance.

*Defined as time from randomization until the date of objective intracranial disease progression or death, whichever comes first, based on BICR using RECIST v1.1. Specifically, intracranial disease progression is defined as having progression of brain metastases or occurrence of new brain lesion.7

At 12 months, 50% of patients remained intracranial progression-free on RYBREVANT® + chemotherapy and 34% on chemotherapy alone

For previously treated adult patients with locally advanced or metastatic EGFR+ NSCLC

Intracranial ORR in patients with baseline intracranial disease1

improvement in intracranial PFS in the ITT populationimprovement in intracranial PFS in the ITT population Mobile

Data were only available for intracranial CRs and not available for intracranial PRs.

This was a prespecified analysis and was not powered to show statistical significance.

~3X icORR with RYBREVANT® + chemotherapy

BICR, blinded independent central review; icORR, intracranial overall response rate; icPFS, intracranial progression-free survival; NE, not estimable; ORR, overall response rate; OS, overall survival; RECIST, Response Evaluation Criteria in Solid Tumors.

Study Design

For previously treated adult patients with locally advanced or metastatic EGFR+ NSCLC

MARIPOSA-2: The first approved EGFR-targeting therapy in combination with chemotherapy post-osimertinib1,3

MARIPOSA-2 is a randomized, open-label, multicenter, Phase 3 trial. Eligible patients were required to have locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations and progressive disease on or after receiving osimertinib. Patients with asymptomatic or previously treated and stable intracranial metastases were eligible to enroll. Patients were randomized (1:2:2) to receive RYBREVANT in combination with carboplatin and pemetrexed (N=131), carboplatin and pemetrexed (N=263), or RYBREVANT® as part of another combination regimen. The evaluation of efficacy for metastatic NSCLC relied upon comparison between RYBREVANT® in combination with chemotherapy and chemotherapy alone.

Full Study DetailsFull Study Details Mobile

Baseline characteristics were well-balanced across treatment types3

Baseline CharacteristicsBaseline Characteristics Mobile

*Other includes Black or African American, American Indian or Alaska Native, multiple, unknown, and not reported.

DOR, duration of response.

Safety

Infusion-Related Reactions

Based on the pooled safety population (N=281), IRR occurred in 50% of patients treated with RYBREVANT® in combination with carboplatin and pemetrexed, including Grade 3 (3.2%) adverse reactions. The incidence of infusion modifications due to IRR was 46%, and 2.8% of patients permanently discontinued RYBREVANT® due to IRR.

Interstitial Lung Disease/Pneumonitis

Based on the pooled safety population (N=281), ILD/pneumonitis occurred in 2.1% of patients treated with RYBREVANT® in combination with carboplatin and pemetrexed, with 1.8% of patients experiencing Grade 3 ILD/pneumonitis. 2.1% of patients discontinued RYBREVANT® due to ILD/pneumonitis.

Dermatologic Adverse Reactions

Based on the pooled safety population (N=281), rash occurred in 82% of patients treated with RYBREVANT® in combination with carboplatin and pemetrexed, including Grade 3 (15%) adverse reactions. Rash leading to dose reductions occurred in 14% of patients, and 2.5% permanently discontinued RYBREVANT® and 3.1% discontinued pemetrexed.

Ocular Toxicity

Based on the pooled safety population (N=281), ocular toxicity occurred in 16% of patients treated with RYBREVANT® in combination with carboplatin and pemetrexed. All events were Grade 1 or 2.

Embryo-Fetal Toxicity

Based on its mechanism of action and findings from animal models, RYBREVANT® can cause fetal harm when administered to a pregnant woman. Administration of other EGFR inhibitor molecules to pregnant animals has resulted in an increased incidence of impairment of embryo-fetal development, embryo lethality, and abortion. Advise females of reproductive potential of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of RYBREVANT®.

*The pooled safety population described in Warnings and Precautions reflects exposure to RYBREVANT® in combination with carboplatin and pemetrexed in 281 patients in both the MARIPOSA-2 (n=130) and the PAPILLON (n=151) studies.

Safety profile of RYBREVANT® + chemotherapy in the MARIPOSA-2 study1

Majority of ARs were Grades 1 and 2

ARs (≥10%) in patients in MARIPOSA-2

Adverse Reaction TableAdverse Reaction Table Mobile
  • Serious ARs occurred in 32% of patients who received RYBREVANT® + chemotherapy and 20% of patients who received chemotherapy alone1,3
  • Serious ARs in >2% of patients were included dyspnea (3.1%), thrombocytopenia (3.1%), sepsis (2.3%), and pulmonary embolism (2.3%)1
  • Fatal ARs occurred in 2.3% of patients who received RYBREVANT® + chemotherapy and 1% of patients who received chemotherapy alone1,3
  • The most common ARs (occurring in ≥20% of patients) were rash, IRRs, fatigue, nail toxicity, nausea, constipation, edema, stomatitis, decreased appetite, musculoskeletal pain, vomiting, and COVID-191
  • Clinically relevant ARs in <10% of patients who received RYBREVANT® + chemotherapy include abdominal pain, hemorrhoids, dizziness, visual impairment, trichomegaly, keratitis, and ILD1

Select laboratory abnormalities (≥20%) that worsened from baseline in MARIPOSA-21

Lab AbnormalitiesLab Abnormalities Mobile

Based on the pooled safety population (N=281), the most common Grade 3 to 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.

In the MARIPOSA-2 study, most IRRs occured during the first infusion (Week 1, Day 1) and rarely during subsequent infusions5

IRRIRR Mobile
  • 91% of IRRs were Grades 1-2
  • Median time to onset of first IRR was 1 hour (range 0.02-13.5 hours)
  • Monitor patients for any signs and symptoms of IRRs during RYBREVANT® infusion in a setting where cardiopulmonary resuscitation medication and equipment are available. Interrupt infusion if IRR is suspected. Reduce the infusion rate or permanently discontinue RYBREVANT® based on severity
  • Signs and symptoms of IRR include dyspnea, flushing, fever, chills, nausea, chest discomfort, hypotension, and vomiting

AR, adverse reaction; ILD, interstitial lung disease; IRR, infusion-related reaction.

Discontinuation Rates and Dose Modifications

~90% of patients treated with RYBREVANT® + chemotherapy were able to stay on treatment without AR-related discontinuation

11% of patients permanently discontinued RYBREVANT® due to ARs1

  • Most frequent ARs leading to treatment discontinuation in ≥5% of patients were IRRs1

Dose interruptions of RYBREVANT® due to an AR occurred in 60% of patients1

  • IRRs requiring infusion interruptions occurred in 52% of patients
  • ARs requiring dose interruption in ≥5% of patients included IRR, rash, and fatigue

Dose reductions of RYBREVANT® due to an AR occurred in 17% of patients1

  • ARs requiring dose reductions in ≥2% of patients included rash

See therapy management for information on strategies to proactively address ARs

Learn more

References:

  1. RYBREVANT® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
  2. RYBREVANT® (amivantamab-vmjw) plus standard of care approved in the U.S. as first and only targeted regimen to cut risk of disease progression by more than half in second- line EGFR-mutated advanced lung cancer. Johnson & Johnson. September 19, 2024.
    https://www.jnj.com/media-center/press-releases/rybrevant-amivantamab-vmjw-plus-standard-of-care-approved-in-the-u-s-as-first-and-only-targeted-regimen-to-cut-risk-of-disease-progression-by-more-than-half-in-second-line-egfr-mutated-advanced-lung-cancer
  3. Passaro A, Wang J, Wang Y, et al; MARIPOSA-2 Investigators. 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.
  4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.9.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed September 9, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
  5. Data on file. Janssen Biotech, Inc.
  6. Popat S, Reckamp KL, Califano R, et al. Amivantamab plus chemotherapy vs chemotherapy in EGFR-mutated, advanced non-small cell lung cancer after disease progression on osimertinib. Presented at: European Society for Medical Oncology Congress; September 13-17, 2024; Barcelona, Spain.
  7. Passaro A, Wang J, Wang Y, et al; MARIPOSA-2 Investigators. 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. Supplementary Appendix. Ann Oncol. 2024;35(1):77-90.