Primary Endpoint

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

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

RYBREVANT® + chemotherapy (carboplatin/pemetrexed) reduced the risk of progression or death by 52%1,2

RYBREVANT® + chemotherapy (carboplatin/pemetrexed) reduced the risk of progression or death by 52% graphRYBREVANT® + chemotherapy (carboplatin/pemetrexed) reduced the risk of progression or death by 52% graph
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 alone2
  • At 6 months: 51% of patients were progression-free with RYBREVANT® + chemotherapy vs 30% of patients with chemotherapy alone2
  • At 12 months: 22% of patients were progression-free with RYBREVANT® + chemotherapy vs 13% of patients with chemotherapy alone2
MARIPOSA-2 study design

NCCN PREFERRED AFTER OSIMERTINIB3

Amivantamab* (RYBREVANT FASPRO™ or RYBREVANT®) + chemotherapy† is the ONLY NCCN Category 1 (preferred) treatment option for patients with EGFR+‡ nonsquamous mNSCLC progressing on osimertinib who are symptomatic with multiple systemic lesions according to the National Comprehensive Cancer Network® (NCCN®).

*Amivantamab includes both amivantamab and hyaluronidase-lpuj (RYBREVANT FASPRO™) subcutaneous injection and IV amivantamb-vmjw (RYBREVANT®). Amivantamab and hyaluronidase-lpuj has different dosing and administration instructions compared with IV amivantamab-vmjw.

†Chemotherapy is carboplatin and pemetrexed.3

‡EGFR exon 19 deletion or exon 21 L858R mutations.3

PFS across patient subgroups2

PFS across patient subgroups in MARIPOSA-2 clinical trialPFS across patient subgroups in MARIPOSA-2 clinical trial

This was a prespecified analysis (except for EGFR mutation type) and was not powered to show statistical significance.

CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; ex19del, exon 19 deletion; HR, hazard ratio; IV, intravenous; mNSCLC, metastatic non–small cell lung cancer; 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 rates1,4

RYBREVANT® + chemotherapy overall response rates in MARIPOSA-2 clinical trial graph: RYBREVANT® + chemotherapy 53% vs chemotherapy 29%RYBREVANT® + chemotherapy overall response rates in MARIPOSA-2 clinical trial graph: RYBREVANT® + chemotherapy 53% vs chemotherapy 29%

~2X ORR with RYBREVANT® + chemotherapy compared with chemotherapy alone1

Median duration of response1,4

Median duration of response in MARIPOSA-2 clinical trial graph: RYBREVANT® + chemotherapy 6.9 months vs chemotherapy 5.6 monthsMedian duration of response in MARIPOSA-2 clinical trial graph: RYBREVANT® + chemotherapy 6.9 months vs chemotherapy 5.6 months

32% of patients with RYBREVANT® + chemotherapy had a response of ≥6 months and 20% with chemotherapy alone4

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 overall survival results1

MARIPOSA-2 clinical trial interim overall survival results: HR=0.73

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.

Intracranial PFS2*

RYBREVANT® + chemotherapy median icPFS was 12.5 months (95% CI: 10.8, NE) and 8.3 months (95% CI: 7.3, 11.3) for chemotherapy alone2

MARIPOSA-2 clinical trial intracranial PFS graph, improved results vs chemotherapy alone shown at 6 months and 12 months.MARIPOSA-2 clinical trial intracranial PFS graph, improved results vs chemotherapy alone shown at 6 months and 12 months.

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 metastasis or occurrence of new brain lesion.5

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

Intracranial ORR in patients with baseline intracranial disease1

Intracranial ORR graph: RYBREVANT® + chemotherapy 20% vs chemotherapy 7%Intracranial ORR graph: RYBREVANT® + chemotherapy 20% vs chemotherapy 7%

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® + chemotherapy1

NCCN PREFERRED THERAPY FOR BRAIN METASTASES6,7

Amivantamab-vmjw (RYBREVANT®)-based regimens* including amivantamab-vmjw (RYBREVANT®) + carboplatin + pemetrexed are the only NCCN preferred combination treatment options for brain metastases in patients with EGFR+† mNSCLC.‡

*Including but not limited to amivantamab-vmjw + carboplatin + pemetrexed.6

†EGFR exon 19 deletion or exon 21 L858R mutations.6

‡See the current NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for detailed recommendations, including other treatment options.

BICR, blinded independent central review; CR, complete response; icORR, intracranial overall response rate; icPFS, intracranial progression-free survival; NE, not estimable; OR, odds ratio; ORR, overall response rate; OS, overall survival; PR, partial response; 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-osimertinib1,2

MARIPOSA-2 is an open-label, multicenter, phase 3 trial. Patients with asymptomatic or previously treated and stable intracranial metastases were eligible to enroll. The evaluation of efficacy relied upon comparison between RYBREVANT® in combination with chemotherapy and chemotherapy alone.

Serial brain MRIs were
required for all patients

KEY ELIGIBILITY CRITERIA

  • Locally advanced or metastatic NSCLC
  • Progressed on or after osimertinib monotherapy
    (as most recent line)
  • Documented EGFR ex19del or L858R
  • ECOG PS 0 or 1
  • Asymptomatic or previously treated and stable intracranial metastases
1:2:2

RANDOMIZATION (N=657)

RYBREVANT®
+ chemotherapy
(n=131)

Chemotherapy
(n=263)

Data
set under
investigation

RYBREVANT® as part of
another combination
regimen (n=263)

PRIMARY ENDPOINT:
PFS BY BICR PER RECIST V1.1 FOR

  • RYBREVANT® + chemotherapy vs chemotherapy

SECONDARY ENDPOINTS

  • ORR by BICR
  • DOR by BICR
  • OS
  • Intracranial PFS by BICR
  • Safety
Chemotherapy regimen included carboplatin
and pemetrexed
Serial brain MRIs were
required for all patients

KEY ELIGIBILITY CRITERIA

  • Locally advanced or metastatic NSCLC
  • Progressed on or after osimertinib monotherapy
    (as most recent line)
  • Documented EGFR ex19del or L858R
  • ECOG PS 0 or 1
  • Asymptomatic or previously treated and stable intracranial metastases
1:2:2

RANDOMIZATION (N=657)

RYBREVANT®
+ chemotherapy
(n=131)

Chemotherapy
(n=263)

Data
set under
investigation

RYBREVANT® as part of
another combination
regimen (n=263)

Chemotherapy regimen included carboplatin
and pemetrexed

PRIMARY ENDPOINT:
PFS BY BICR PER RECIST V1.1 FOR

  • RYBREVANT® + chemotherapy vs chemotherapy

SECONDARY ENDPOINTS

  • ORR by BICR
  • DOR by BICR
  • OS
  • Intracranial PFS by BICR
  • Safety

Baseline characteristics were well-balanced across treatment types2

Characteristic
RYBREVANT® + chemotherapy (N=131)
Chemotherapy (N=263)
Median age, years (range)
62 (36–84)
62 (31–85)
Female, n (%)
81 (62)
157 (60)
Race, n (%)
Asian
63 (48)
127 (48)
White
60 (46)
123 (47)
Other*
8 (6)
13 (5)
ECOG PS 1, n (%)
76 (58)
162 (62)
History of smoking, n (%)
41 (31)
95 (36)
History of brain metastases, n (%)
58 (44)
120 (46)
No prior brain radiation
24 of 58 (41)
61 of 120 (51)
Previous osimertinib line of therapy, n (%)
First
97 (74)
181 (69)
Second
34 (26)
82 (31)
EGFR mutation type, n (%)
Ex19del
89 (68)
183 (70)
L858R
42 (32)
79 (30)

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

DOR, duration of response; MRI, magnetic resonance imaging.

Safety

Majority of ARs in the MARIPOSA-2 trial were grades 1 and 21

ARs (≥10%) in patients in MARIPOSA-21

Adverse reaction
RYBREVANT® + chemotherapy (N=130)
Chemotherapy (N=243)
All grades (%)
Grades 3–4 (%)
All grades (%)
Grades 3–4 (%)
Skin and subcutaneous tissue disorders
Rash*
72
11
12
0
Nail toxicity*
45
2.3
0.4
0
Pruritus
15
0
7
0
Dry skin*
15
0
2.5
0
General disorders and administration site conditions
Infusion-related reaction
59
5.4
0.4
0
Fatigue*
51
3.8
35
3.7
Edema*
36
1.5
11
0.4
Pyrexia
12
0
10
0
Gastrointestinal disorders
Nausea
45
0.8
37
0.8
Constipation
39
0.8
30
0
Stomatitis*
35
2.3
11
0
Vomiting
25
0.8
17
0.4
Diarrhea*
15
1.5
7
0.8
Metabolism and nutrition disorders
Decreased appetite
31
0
21
1.2
Musculoskeletal and connective tissue disorders
Musculoskeletal pain*
30
3.1
19
0.8
Infections and infestations
COVID-19
21
1.5
10
0
Eye disorders
Ocular toxicity*
17
0
3.7
0
Vascular disorders
Hemorrhage*
14
0.8
4.9
0
Venous thromboembolism*
10
2.3
4.5
2.9
Respiratory, thoracic, and mediastinal disorders
Cough*
14
0
16
0.4
Dyspnea*
13
1.5
8
1.2

*Grouped terms.

  • Serious ARs occurred in 32% of patients who received RYBREVANT® + chemotherapy and 20% of patients who received chemotherapy alone1,2
  • Serious ARs in >2% of patients 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 alone1,2
  • The most common ARs (≥20%) 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 included abdominal pain, hemorrhoids, dizziness, visual impairment, trichomegaly, keratitis, ILD, and skin ulcer1

Learn about the safety profile of RYBREVANT FASPRO™

Learn more

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

Laboratory abnormality
RYBREVANT® + chemotherapy (N=130)
Chemotherapy (N=243)
All grades (%)
Grades 3–4 (%)
All grades (%)
Grades 3–4 (%)
Hematology
Decreased white blood cells
91
42
85
19
Decreased neutrophils
74
49
64
25
Decreased platelets
74
17
58
9
Decreased hemoglobin
71
12
77
9
Decreased lymphocytes
69
28
58
18
Chemistry
Decreased albumin
73
3.8
26
0.4
Decreased sodium
49
11
30
6
Increased aspartate aminotransferase
47
0.8
52
0.9
Increased alkaline phosphatase
42
0
29
0.4
Increased alanine aminotransferase
39
3.9
56
6
Decreased magnesium
38
0.8
17
0.4
Decreased potassium
37
11
12
3.4
Increased gamma-glutamyl transferase
30
3.1
41
1.3
Decreased calcium (corrected)
25
0
11
0.9

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.1

In the MARIPOSA-2 trial, most IRRs occurred during the first infusion (week 1, day 1) and rarely during subsequent infusions4

IRR rates in the MARIPOSA-2 clinical trialIRR rates in the MARIPOSA-2 clinical trial
  • 91% of IRRs were grades 1 and 24
  • Median time to onset of first IRR was 1 hour (range, 0.02–13.5 hours)4
  • 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 severity7
  • If an anaphylactic reaction occurs, permanently discontinue RYBREVANT®7
  • Signs and symptoms of IRR include dyspnea, flushing, fever, chills, nausea, chest discomfort, hypotension, and vomiting7

Prophylaxis may reduce the risk of IRRs and dermatologic ARs

Learn more

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

Dose Modifications and Discontinuation Rates

Adaptable dosing is available to help your patients manage ARs and stay on treatment4*

Most patients used dose modification to continue treatment with RYBREVANT®.1
  • Permanent discontinuation of RYBREVANT® due to an AR occurred in 11% of patients
  • Dose interruption due to an AR occurred in 60% of patients
  • Dose reductions due to an AR occurred in 17% of patients

Learn more about available adaptable dosing

Learn more

*Certain types and severity of ARs require discontinuation after first occurrence.1

1L, first-line.

References:

  1. RYBREVANT FASPRO™ [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
  2. 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. doi:10.1016/j.annonc.2023.10.117
  3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.4.2026. © National Comprehensive Cancer Network, Inc. 2026. All rights reserved. Accessed March 6, 2026. 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.
  4. Data on file. Janssen Biotech, Inc.
  5. 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)(suppl):S1-S36. doi:10.1016/j.annonc.2023.10.117
  6. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Central Nervous System Cancers V.3.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed December 5, 2025. 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.
  7. RYBREVANT® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.