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
• Safety data were not separately reported by age in the RYBREVANT phase 3 studies but were reported in the CHRYSALIS study summarized below.
• MARIPOSA (NCT04487080) is an ongoing, phase 3, randomized study evaluating 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 patients with EGFR-mutated (Exon 19 deletion [Exon19del] or Exon 21 L858R substitution) locally advanced or metastatic NSCLC.^2-4
  • For patients treated with RYBREVANT plus lazertinib vs osimertinib, the hazard ratio (HR) for progression-free survival (PFS) by blinded independent central review (BICR) was 0.5 (95% confidence interval [CI], 0.39-0.65), 1.06 (95% CI, 0.8-1.41), 0.7 (95% CI, 0.57-0.85), and 0.77 (95% CI, 0.46-1.3) in those aged <65, ≥65, <75, and ≥75 years, respectively (Table: MARIPOSA: BICR-Assessed PFS by Age).⁴
• 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.^5,6
  • For patients treated with RYBREVANT plus chemotherapy vs chemotherapy alone, the HR for PFS by BICR was 0.37 (95% CI, 0.26-0.53) and 0.44 (95% CI, 0.27-0.7) in those aged <65 and ≥65 years, respectively (Table: PAPILLON: BICR-Assessed PFS by Age).⁶
• 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.^7,8
  • For patients treated with RYBREVANT-lazertinib-chemotherapy vs chemotherapy alone, the HR for PFS by BICR was 0.47 (95% CI, 0.35-0.64) and 0.41 (95% CI, 0.28-0.6) in those aged <65 and ≥65 years, respectively. For patients treated with RYBREVANT-chemotherapy vs chemotherapy alone, the HR for PFS by BICR was 0.44 (95% CI, 0.31-0.64) and 0.61 (95% CI, 0.4-0.94) in those aged <65 and ≥65 years, respectively (Table: MARIPOSA-2: BICR-Assessed PFS by Age).⁸
• 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.^9,10 Safety and efficacy were evaluated in 114 and 81 patients, respectively.¹⁰
  • In the efficacy population, the overall response rate (ORR) by BICR was 44% (95% CI, 30-59) and 33% (95% CI, 18-52) in those aged <65 and ≥65 years, respectively (Table: CHRYSALIS: BICR-Assessed ORR by Age).¹⁰
  • In a long-term analysis of 114 patients in CHRYSALIS cohort D with a median follow-up of 19.2 months,¹¹ the investigator-assessed ORR in those aged ≥65 and ≥75 years was 32% and 33%, respectively.¹²
  • The most frequent treatment-emergent adverse event (AE) of clinical importance in both age subgroups was rash, followed by infusion-related reactions, which were reported at a higher rate among patients <65 years than among those ≥65 years (89.6% vs 80.9% and 71.6% vs 57.4%, respectively; Table: CHRYSALIS: Treatment-Emergent AEs by Age (<65 and ≥65 Years) in Patients Treated at the RP2D).¹³

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 Exon 21 L858R substitution) locally advanced or metastatic NSCLC.^2-4

Results

Efficacy

• The median followup was 22 months.⁴
• The BICR-assessed PFS by age (<65, ≥65, <75, and ≥75 years) reported as a subgroup analysis in the MARIPOSA study is shown in the table below.

Safety

• Safety results have not been reported by age in the MARIPOSA study.

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.^5,6

Results

Efficacy

• The median followup was 14.9 months.⁶
• The BICR-assessed PFS by age (<65 and ≥65 years) reported as a subgroup analysis in the PAPILLON study is shown in the table below.

Safety

• Safety results have not been reported by age in the PAPILLON study.

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).^7,8
• In the RYBREVANT-lazertinib-chemotherapy arm, patients randomized before November 7, 2022, received lazertinib on cycle 1 day 1.^7,8 Due to an increase in hematologic and gastrointestinal toxicities in the arm, the regimen was modified to start lazertinib after carboplatin completion.⁸
  • An open-label, randomized, extension cohort will evaluate the efficacy and safety of the modified RYBREVANT-lazertinib-chemotherapy regimen vs RYBREVANT-chemotherapy.⁸

Results

Efficacy

• The median followup was 8.7 months.⁸
• The BICR-assessed PFS by age (<65 and ≥65 years) reported as a subgroup analysis in the MARIPOSA-2 study is shown in the table below.

Safety

• Safety results have not been reported by age in the MARIPOSA-2 study.

CHRYSALIS Study

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 efficacy and 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 recommended phase 2 dose (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.^9,10
  • 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.¹⁰

Results

Efficacy

• The median followup was 9.7 months (range, 1.1-29.3).¹⁰
• The BICR-assessed ORR by age (<65 and ≥65 years) reported as a subgroup analysis in the CHRYSALIS study is shown in the table below.

• In a long-term analysis of 114 patients in CHRYSALIS cohort D with a median follow-up of 19.2 months, the investigator-assessed ORR was 36.8% (95% CI, 28.0-46.4).¹¹
  • Among patients aged ≥65 and ≥75 years, the investigator-assessed ORR was 32% and 33%, respectively.¹²

Safety

• The median follow-up was 5.1 months (range, 0.2-29.3).¹⁰
• The incidence of treatment-emergent AEs by age (<65 and ≥65 years) reported as a subgroup analysis in the CHRYSALIS study is shown in the table below.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and DerwentDrug File (and/or other resources, including internal/external databases) was conducted on 26 July 2024.