SUMMARY

• 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
• MARIPOSA (NCT04487080) is an ongoing, phase 3, randomized study evaluating the efficacy and safety of RYBREVANT and lazertinib combination therapy (open-label, n=429) vs osimertinib (double-blind, n=429) vs lazertinib (double-blind, n=216) as first-line treatment in patients with EGFR-mutated (Exon 19 deletion [Exon19del] or Exon 21 L858R substitution) locally advanced or metastatic NSCLC.^2-4
  • Among patients treated with RYBREVANT plus lazertinib, treatment-emergent administration site and infusion site extravasation was reported in 2 (0.5%) patients each (grade 1, n=1; grade 2, n=1 for each); and infusion site extravasation in 2 (0.5%) patients in the osimertinib group (both grade 2; Table: MARIPOSA: Incidence of Extravasation).⁵
• 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; n=153) vs chemotherapy alone (carboplatin and pemetrexed; n=155) in patients with untreated locally advanced or metastatic NSCLC and EGFR Exon 20 insertion (Exon20ins) mutations.^6,7
  • Among patients treated with RYBREVANT plus chemotherapy, a grade 1 treatment-emergent administration site extravasation was reported in 1 (0.6%) patient (Table: PAPILLON: Incidence of Extravasation).⁸
• MARIPOSA-2 (NCT04988295) is an ongoing, phase 3, randomized, open-label study designed to assess the efficacy and safety of RYBREVANT-lazertinib-chemotherapy (pemetrexed and carboplatin; n=263) and RYBREVANT-chemotherapy (pemetrexed and carboplatin; n=131) vs chemotherapy alone (pemetrexed and carboplatin; n=263) in patients with EGFR-mutated (Exon19del or Exon 21 L858R substitution) locally advanced or metastatic NSCLC on or after osimertinib monotherapy.^9,10
  • Among patients treated with RYBREVANT-lazertinib-chemotherapy, treatment-emergent extravasation was reported in 2 (0.8%) patients (grade 1, n=1; grade 2, n=1; Table: MARIPOSA-2: Incidence of Extravasation).¹¹
• CHRYSALIS (NCT02609776) is an ongoing phase 1, open-label, multicenter, dose escalation and dose expansion study evaluating the safety, efficacy, and pharmacokinetics of RYBREVANT as monotherapy and in combination with other therapies in adult patients with advanced NSCLC harboring EGFR mutations who had disease progression during or after previous standard of care (SOC) treatment.¹²
  • Among 114 patients in the safety population, there were no reports of extravasation (Table: CHRYSALIS: Incidence of Extravasation in Patients Treated at the RP2D).¹³
  • Among 258 patients treated at the recommended phase 2 dose (RP2D), treatment-emergent extravasation and infusion site extravasation were reported in 1 patient each. None of the events were considered related to RYBREVANT.¹³
• There is no official designation for RYBREVANT being classified as a vesicant or irritant. There has not been any evidence that RYBREVANT is a vesicant or irritant. In clinical and nonclinical studies, irritant and vesicant inducing effects related to RYBREVANT have not been detected in repeated dosing of RYBREVANT intravenously (IV) in humans or IV and subcutaneous (SC) dosing in non-human primates.¹⁴
• If extravasation occurs, manage according to standard institutional practice.
• Please refer to RYBREVANT product labeling for complete safety information, including dose modification guidelines for adverse reactions.
• Please refer to product labeling for carboplatin and/or pemetrexed for complete prescribing information.

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.

CLINICAL DATA

MARIPOSA Study

Study Design/Methods

• Phase 3, ongoing, randomized study designed to assess the efficacy and safety of RYBREVANT plus lazertinib (open-label, n=429) vs osimertinib (double-blind, n=429) vs lazertinib (double-blind, n=216) as first-line treatment in 1074 patients with EGFRmutated (Exon19del or L858R) locally advanced or metastatic NSCLC.^2-4
  • RYBREVANT 1050 mg IV (1400 mg IV for body weight ≥80 kg) was administered every week for the first 4 weeks, with the initial dose as a split infusion on cycle 1 day 1 (C1D1) and D2, followed by every 2 weeks thereafter.
  • Lazertinib 240 mg was administered orally (PO) once daily.
  • Osimertinib 80 mg PO was administered once daily.

Results

• The median duration of treatment was 18.5 months for RYBREVANT plus lazertinib and 18 months for osimertinib.⁴
• The incidence of extravasation reported in the MARIPOSA study is shown in the table below.

PAPILLON Study

Study Design/Methods

• Phase 3, ongoing, randomized, open-label study designed to compare the efficacy and safety of RYBREVANT plus chemotherapy (carboplatin and pemetrexed; n=153) vs chemotherapy alone (carboplatin and pemetrexed; n=155) in patients with untreated locally advanced or metastatic NSCLC and EGFR Exon20ins mutations.^6,7
  • RYBREVANT 1400 mg IV (1750 mg IV for body weight ≥80 kg) was administered every week for the first 4 weeks, with the initial dose as a split infusion on C1D1 and D2, followed by RYBREVANT 1750 mg IV (2100 mg IV for body weight ≥80 kg) every 3 weeks starting at week 7 (C3D1) until disease progression.
  • Pemetrexed 500 mg/m² IVwas administered every 3 weeks until disease progression.¹⁵
  • Carboplatin area under the curve (AUC) 5 IV was administered every 3 weeks for up to 4 cycles.

Results

• The median duration of treatment was 9.7 months (range, 0.1-26.9) for RYBREVANT plus chemotherapy and 6.7 months (range, 0-25.3) for chemotherapy alone.^6,7
• The incidence of extravasation reported in the PAPILLON study is shown in the table below.

MARIPOSA-2 Study

Study Design/Methods

• Phase 3, ongoing, randomized, open-label study designed to assess the efficacy and safety of RYBREVANT-lazertinib-chemotherapy (n=263) and RYBREVANT-chemotherapy (n=131) vs chemotherapy alone (n=263) in 657 patients with EGFR-mutated locally advanced or metastatic NSCLC on or after osimertinib monotherapy (as the most recent line of therapy).^9,10
  • RYBREVANT 1400 mg IV (1750 mg IV for body weight ≥80 kg) was administered every week for the first 4 weeks, with the initial dose as a split infusion on C1D1 and D2, followed by 1750 mg IV (2100 mg IV for body weight ≥80 kg) every 3 weeks starting at week 7 (C3D1) until disease progression.
  • Lazertinib 240 mg PO was administered once daily.
  • Chemotherapy was administered every 3 weeks at the beginning of each cycle, with carboplatin at AUC 5 IV for the first 4 cycles, and pemetrexed at 500 mg/m² IV until disease progression.
• In the RYBREVANT-lazertinib-chemotherapy arm, patients randomized before November 7, 2022 received lazertinib on C1D1. Due to an increase in hematologic and gastrointestinal toxicities in the arm, the regimen was modified to start lazertinib after carboplatin completion.¹⁰
  • An open-label, randomized, extension cohort will evaluate the efficacy and safety of the modified RYBREVANT-lazertinib-chemotherapy regimen vs RYBREVANT-chemotherapy.

Results

• At a median follow-up of 8.7 months, the median duration of treatment was 5.8 months for RYBREVANT-lazertinib-chemotherapy, 6.3 months for RYBREVANT-chemotherapy, and 3.7 months for chemotherapy alone.^9,10
• The incidence of extravasation reported in the MARIPOSA-2 study is shown in the table below.
• Of the 2 extravasation events reported in the RYBREVANT-lazertinib-chemotherapy arm¹¹:
  • One was a grade 2 infusion-related reaction (IRR) event deemed unrelated to RYBREVANT that did not require any RYBREVANT dose modification.
  • One was a grade 1 RYBREVANT-related event that led to RYBREVANT dose interruption.

CHRYSALIS Study

The results of the CHRYSALIS study are also included in the RYBREVANT product labeling. The incidence of adverse reactions described below may vary from that in the RYBREVANT product labeling due to the evaluation of different patient populations for safety analyses, contributing to differences in reported percentages. The summary below describes safety results from patients with metastatic or unresectable NSCLC and EGFR Exon20ins mutations with disease progression during or after platinum-based chemotherapy who received RYBREVANT at the RP2D and all patients treated at the RP2D.

Study Design/Methods

• Phase 1, ongoing, open-label, multicenter, dose escalation and dose expansion study evaluating the safety, efficacy, and pharmacokinetics of RYBREVANT as monotherapy and in combination with other therapies in adult patients with advanced NSCLC harboring EGFR mutations who had disease progression during or after previous SOC treatment.¹²
  • RYBREVANT monotherapy was administered at the RP2D: 1050 mg IV (1400 mg IV for body weight ≥80 kg) every week for C1, with the initial dose as a split infusion on C1D1 and D2, and every 2 weeks thereafter until disease progression or unacceptable toxicity.
  • A total of 114 patients with metastatic or unresectable NSCLC and EGFR Exon20ins mutations with disease progression during or after platinum-based chemotherapy were evaluated for safety, and 81 evaluable patients were assessed for efficacy.

Results

• The median follow-up for safety was 5.1 months (range, 0.2-29.3 months).¹²
• The incidence of treatment-emergent adverse events of extravasation and infusion site extravasation are shown in the table below. There were no reports of extravasation events in the safety population. None of the extravasation events reported in the 258 patients treated at the RP2D were considered related to RYBREVANT.¹³

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and DerwentDrug File (and/or other resources, including internal/external databases) was conducted on 11 June 2024.