For APPs & Nurses

Primary Endpoint

For first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations

The first and only targeted therapy to show statistically significant PFS improvements1

RYBREVANT® + chemotherapy demonstrated a statistically significant reduction in the risk of progression or death by 60% vs chemotherapy alone, as assessed by BICR1,2

RYBREVANT® (amivantamab) and chemotherapy progression-free rates in Papillon trialPapillon trial progress-free rates for RYBREVANT® and chemotherapy

~2X mPFS: 11.4 months (95% CI: 9.8, 13.7) with RYBREVANT® + chemotherapy vs 6.7 months (95% CI: 5.6, 7.3) with chemotherapy alone1

PAPILLON study design

PFS results in prespecified subgroups2

RYBREVANT® (amivantamab) and chemotherapy PFS benefits across patient subgroups in Papillon trialPapillon trial disease progression rates for RYBREVANT® and chemotherapy

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

RYBREVANT® is also approved for patients with EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy1

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BICR, blinded independent central review; CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; HR, hazard ratio; mPFS, median progression-free survival; NSCLC, non–small cell lung cancer; PFS, progression-free survival.

Other Endpoints

Interim OS results

OS results were immature at the current analysis (44% of prespecified events); no trend towards a detriment was observed1

  • 48% of the treated patients crossed over from the carboplatin and pemetrexed arm after confirmation of disease progression to receive RYBREVANT® as a single agent1

At the interim analysis (33% of prespecified events), OS results were2:

RYBREVANT® and chemotherapy survival rates in Papillon trialRYBREVANT® (amivantamab) and chemotherapy survival rates in Papillon trial

For first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations

Unprecedented responses from a novel first-line regimen

RYBREVANT® + chemotherapy demonstrated higher responses as assessed by BICR. Deep and fast responses were also observed1,3

RYBREVANT® and chemotherapy response rates in the Papillon trialRYBREVANT® (amivantamab) response rates in the Papillon trial for RYBREVANT® and chemotherapy

Depth

  • CR was 4% with RYBREVANT® + chemotherapy and 1% with chemotherapy alone1

Speed of Response

  • Median TTR was 6.7 weeks (range, 5.1 to 72.5) with RYBREVANT® + chemotherapy and 11.4 weeks (range, 5.1 to 60.2) with chemotherapy alone2

Time to response was not a prespecified analysis and both CR and TTR was not powered to show statistical significance.

RYBREVANT® + chemotherapy demonstrated durable responses as assessed by BICR4

Papillon RYBREVANT® and chemotherapy response rates compared to chemotherapy response ratesRYBREVANT® (amivantamab) and chemotherapy response rates in Papillon trial

This was a prespecified analysis and was not powered for statistical significance.

~2X median DOR1

Median DOR is 10.1 months (95% CI: 8.5, 13.9) for RYBREVANT® + chemotherapy and 5.6 months (95% CI: 4.4, 6.9) for chemotherapy alone

CR, complete response; DOR, duration of response; ORR, overall response rate; OS, overall survival; TTR, time to response.

Study Design

For adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations

PAPILLON: Evaluating the EGFR-targeting therapy with chemotherapy for first-line EGFR exon 20 insertion mutations1

PAPILLON was a randomized, open-label, multicenter, Phase 3 study in 308 patients, comparing treatment with RYBREVANT® in combination with chemotherapy vs chemotherapy alone in patients with previously untreated, locally advanced or metastatic NSCLC with documented EGFR exon 20 insertion mutations, an ECOG PS of 0 or 1, and adequate organ and bone marrow function.1,2*

Primary Endpoint1,2:

The primary efficacy endpoint was evaluated by PFS according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as evaluated by BICR.

*Patients with definitively treated, clinically stable, asymptomatic brain metastases and off corticosteroids for at least 2 weeks were eligible. Patients with a medical history of ILD or active ILD were excluded.

Treatment with RYBREVANT® + chemotherapy was evaluated in the PAPILLON Phase 3 study1,2

Papillon trial study design for RYBREVANT® and chemotherapyPapillon trial study design for RYBREVANT® and chemotherapy

Patients with definitively treated, clinically stable, asymptomatic brain metastases and off corticosteroids for at least 2 weeks were eligible. Patients with a medical history of ILD or active ILD were excluded.

Baseline characteristics were well-balanced across treatment types2

Papillon trial study design for RYBREVANT® and chemotherapy
Papillon study design characteristics for RYBREVANT® and Chemotherapy

*Race or ethnic group was reported by the patients. In some regions, reporting of race was not required. One patient reported being of multiple races.

†Other includes American Indian or Alaska Native, Black or African American, multiple, or both.

‡Other histologic types included bronchoalveolar carcinoma, non–squamous cell non–small cell lung cancer, and non–small cell carcinoma.

ILD, interstitial lung disease; RECIST, Response Evaluation Criteria in Solid Tumors.

Safety

Infusion-Related Reactions

Based on the pooled safety population (N=281), IRRs 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 PAPILLON study

Majority of ARs were Grades 1 and 21

ARs (≥10%) in patients in PAPILLON

RYBREVANT® (amivantamab) and chemotherapy adverse reactions in Papillon trialRYBREVANT® (amivantamab) and chemotherapy adverse reactions in Papillon trial

*ARs were graded using CTCAE version 5.0.

†Grouped terms.

AR, adverse reaction; CTCAE, Common Terminology Criteria for Adverse Events; IRR, infusion-related reaction.

  • Serious ARs occurred in 37% of patients who received RYBREVANT® + chemotherapy compared with 31% of patients who received chemotherapy alone. Serious ARs in ≥2% of patients included rash, pneumonia, ILD, pulmonary embolism, vomiting, and COVID-191,2
  • Fatal ARs occurred in 4.6% of patients who received RYBREVANT® + chemotherapy and 3% of patients who received chemotherapy alone1,2
  • The most common ARs (≥20%) were rash, nail toxicity, stomatitis, infusion-related reaction, fatigue, edema, constipation, decreased appetite, nausea, COVID-19, diarrhea, and vomiting1
  • Clinically relevant ARs in <10% of patients who received RYBREVANT® + chemotherapy included pulmonary embolism, deep vein thrombosis, skin ulcer, conjunctivitis, and ILD/pneumonitis1

Summary of laboratory abnormalities that worsened from baseline (≥20%) in PAPILLON1

Lab abnormalities observed with RYBREVANT® (amivantamab) and chemotherapy in the Papillon trialRYBREVANT® (amivantamab) laboratory abnormailities observed in the Papillon trial

*ARs were graded using CTCAE version 5.0.

†The denominator used to calculate the rate varied from 113 to 150 based on the number of patients with a baseline value and at least one post-treatment value.

‡The denominator used to calculate the rate varied from 119 to 154 based on the number of patients with a baseline value and at least one post-treatment value.

Grades 3 to 4 laboratory abnormalities (≥2%) were decreased albumin, increased alanine aminotransferase, increased gamma-glutamyl transferase, decreased sodium, decreased potassium, decreased magnesium, and decreases in white blood cells, hemoglobin, neutrophils, platelets, and lymphocytes.1

In the PAPILLON trial, most IRRs occurred during the first infusion (Week 1, Day 1) and rarely during subsequent infusions3

RYBREVANT® (amivantamab) infusion rates in Papillon trialIRRs per RYBREVANT® infusion in Papillon trial
  • 98.7% of IRRs were Grades 1 to 21,3
  • Median time to onset of first IRR was 0.8 hours (0.1 to 3.6 hours)3
  • 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 severity1
  • Signs and symptoms of IRR include dyspnea, flushing, fever, chills, nausea, chest discomfort, hypotension, and vomiting1

Discontinuation Rates and Dose Modifications

~90% of patients treated with RYBREVANT® were able to stay on treatment without AR-related discontinuation1

Permanent discontinuation of RYBREVANT® due to ARs occurred in 11% of patients

ARs resulting in permanent discontinuation of RYBREVANT® in ≥1% of patients were rash and ILD.

Dose interruptions of RYBREVANT®

Dose interruption due to an AR occurred in 64% of patients. ARs requiring dose interruption in ≥5% of patients included rash and nail toxicity.

Infusion interruptions of RYBREVANT®

IRRs requiring infusion interruptions occurred in 38% of patients.

Dose reductions of RYBREVANT®

Dose reductions due to an AR occurred in 36% of patients. ARs requiring dose reductions in ≥5% of patients included rash and nail toxicity.

See Therapy Management for dose modification and reduction information

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References:

  1. RYBREVANT® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
  2. Zhou C, Tang K-J, Cho BC, et al; PAPILLON Investigators. Amivantamab plus chemotherapy in NSCLC with EGFR exon 20 insertions.  N Engl J Med. 2023;389(22):2039-2051.
  3. Data on file. Janssen Biotech, Inc.
  4. Zhou C, Tang K-J, Cho BC, et al; PAPILLON Investigators. Amivantamab plus chemotherapy in NSCLC with EGFR exon 20 insertions.  N Engl J Med. 2023;389(22)(suppl appendix):1-34.