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
• No prospective, randomized trials evaluating the use of RYBREVANT with radiation in metastatic NSCLC were identified in the published literature.
• A real-world study retrospectively evaluated the use of RYBREVANT with or without osimertinib and with or without concurrent radiation therapy in patients with EGFR-mutated NSCLC (N=61).²
  • Of the 61 patients identified in the GEMINI database who received RYBREVANT, 37 (58.7%) received concomitant osimertinib and 25 (39.1%) received concomitant radiation.
  • Among 54 evaluable patients, 23 (43.6%) patients had a clinical response, 9 (16.7%) were clinically stable, and 22 (40.7%) had clinical progression. The overall disease control rate was 59.3%. Efficacy results were not separately reported for patients who received concurrent radiation therapy.
  • Among the 25 patients who received concurrent radiation therapy and were evaluated for safety, the following results were observed:
    • Grade 1 or 2 adverse events (AEs) included infusion reactions (n=12; 48%), rash (n=5; 20%), paronychia (n=5; 20%), fatigue (n=7; 28%), edema (n=4; 17.4%), scalp rash (n=2; 8%), mucositis (n=2; 8%), and nausea (n=4; 10%).³
    • Grade ≥3 AEs were reported in 12 (48%) patients, including infusion reactions (n=3; 12%), rash (n=5; 20%), pneumonitis (n=2; 8%), thrombocytopenia (n=1; 4%), and transaminitis (n=1; 4%).³
    • No neurological toxicities were noted when RYBREVANT was administered with concomitant intracranial radiation. No additional toxicities were noted during radiation to extracranial sites.² 
• A singlecenter retrospective case series evaluated the use of RYBREVANT with intracranial or extracranial radiation therapy in patients with EGFRmutated NSCLC (N=17).⁴ 
  • Radiation was administered concurrently (n=6), prior to (n=6), or after RYBREVANT (n=5). The most common site of radiation while on RYBREVANT was the brain (n=9; 53%) followed by bone (n=6; 35%), along with other extracranial sites including lung (n=1) and lymph nodes (n=1).
  • Median duration of RYBREVANT treatment and median follow‑up were both 9 months (range, 1-21). Median survival from the start of RYBREVANT was 10 months (95% confidence interval, 7.6-12.6).
  • Disease progression occurred intracranially in 5 (29%) patients and extracranially in 10 (59%) patients. Median time to intracranial and extracranial progression was 7.1 months (range, 3-33) and 7.6 months (range, 1-24), respectively.
  • Grade 3 drug‑related pneumonitis was reported in 3 patients (2 with prior systemic therapy; none with prior thoracic radiation). No additional grade ≥3 toxicities were reported, including intracranial radiation necrosis.
• A case of a 57-year-old woman with metastatic lung adenocarcinoma harboring EGFR Exon 20 insertion mutations was reported. After first-line treatment with afatinib and second-line treatment with RYBREVANT 1050 mg intravenous every 2 weeks with dose reduction to 700 mg every 2 weeks for grade 3 paronychia, she received a total of 55 Gray (Gy) hypofractionated chest radiotherapy for a right parahilar lesion and continued RYBREVANT. She further received 19 Gy single-dose radiosurgery for a brain lesion. There was no toxicity, and she continued RYBREVANT beyond the progressive disease.⁵

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 15 January 2026.