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
• 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. The primary endpoint was progression-free survival (PFS) and the secondary endpoints included progression-free survival after first subsequent therapy (PFS2).^2,3
  • PFS was significantly longer in the RYBREVANT plus chemotherapy group than in the chemotherapy group (median, 11.4 months and 6.7 months, respectively; hazard ratio [HR] for disease progression or death, 0.40; 95% confidence interval [CI], 0.30-0.53; P<0.001).³
  • Among all randomized patients, the median PFS2 for RYBREVANT plus chemotherapy vs chemotherapy alone was not estimable (NE; 95% CI, 22.8 months-NE) vs 17.2 months (95% CI, 14-21.5). The HR for disease progression or death was 0.49 (95% CI, 0.32-0.76).⁴
  • Grade ≥3 adverse events (AEs) were reported in 114 (75%) patients treated with RYBREVANT plus chemotherapy and 83 (54%) patients treated with chemotherapy alone. Among patients treated with RYBREVANT plus chemotherapy, the most common (≥10%) grade ≥3 AEs were neutropenia (n=50; 33%), rash (n=17; 11%), leukopenia (n=17; 11%), anemia (n=16; 11%), and thrombocytopenia (n=15; 10%); 10 (7%) patients discontinued RYBREVANT due to RYBREVANT-related AEs.³

CLINICAL DATA

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.^2,3
  • RYBREVANT 1400 mg intravenous (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 cycle 1 day 1 (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.⁵
  • Carboplatin area under the curve (AUC) 5 IV was administered every 3 weeks for up to 4 cycles.

Efficacy: PFS

• PFS was significantly longer in the RYBREVANT plus chemotherapy group than in the chemotherapy group (median, 11.4 months and 6.7 months, respectively; HR for disease progression or death, 0.40; 95% CI, 0.30-0.53; P<0.001).³

Efficacy: PFS2

• 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.^2,3
• Among all randomized patients, the median PFS2 for RYBREVANT plus chemotherapy vs chemotherapy alone was NE (95% CI, 22.8 months-NE) vs 17.2 months (95% CI,
  14-21.5). The HR for disease progression or death was 0.49 (95% CI, 0.32-0.76).⁴

Safety

• Grade ≥3 AEs were reported in 114 (75%) patients treated with RYBREVANT plus chemotherapy and 83 (54%) patients treated with chemotherapy alone.³
• Among patients treated with RYBREVANT plus chemotherapy³:
  • The most common (≥10%) grade ≥3 AEs were neutropenia (n=50; 33%), rash (n=17; 11%), leukopenia (n=17; 11%), anemia (n=16; 11%), and thrombocytopenia (n=15; 10%).
  • AEs leading to discontinuation of all agents were reported in 12 (8%) patients. RYBREVANT discontinuation due to any cause and due to RYBREVANT-related AEs were reported in 17 (11%) and 10 (7%) patients, respectively.
• Among patients treated with chemotherapy alone³:
  • The most common (≥10%) grade ≥3 AEs were neutropenia (n=35; 23%), anemia (n=19; 12%), and thrombocytopenia (n=16; 10%).
  • AEs leading to treatment discontinuation were reported in 12 (8%) patients.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and DerwentDrug File (and/or other resources, including internal/external databases) was conducted on
13 January 2025.