PAPILLON

一行要約

EGFR exon 20 insertion 1L で Amivantamab + chemo が PFS HR 0.40。IO 非感受性の rare driver に対し bispecific + chemo が新標準を確立。

試験デザイン

• 対象: EGFR exon 20 insertion 変異陽性、未治療進行 NSCLC、N=308 (1:1)
• 介入群: Amivantamab 1050/1400mg (体重別) + carboplatin + pemetrexed → amivantamab + pemetrexed 維持
• 対照群: Carboplatin + pemetrexed → pemetrexed 維持
• 層別化: 地域、脳転移有無
• Cross-over: 対照群進行後に amivantamab への cross-over 許容

主要結果

• PFS (primary) : HR 0.40 (95% CI 0.30–0.53, p<0.001)、median 11.4 vs 6.7 mo
• ORR: 73% vs 47%
• DoR: 未到達 vs 4.4 mo
• 主要 AE: Infusion-related reaction 66% (Grade ≥3 3%)、皮疹 49%、paronychia 38%、VTE 13%
• OS: immature (cross-over 影響)

臨床的意義

• EGFR exon 20 insertion 1L standard を amivantamab + chemo に変更 — 従来 chemo ± IO (PFS 約7 mo) からの大幅改善
• EGFR exon 20 ins は classic EGFR-TKI (Osi 含む) に低感受性 → unmet need が大きかった
• MARIPOSA-2 (amivantamab+lazertinib+chemo post-Osi) と共に amivantamab platform を拡張
• VTE リスク管理 (予防的抗凝固) と infusion reaction 対策が実臨床での key

重要論文 Top 10

1. NEJM-2023-Zhou-Amivantamab plus chemotherapy in NSCLC with EGFR exon 20 insertions — PAPILLON primary publication
2. ★★★★★ Park et al. JClinOncol 2021 — CHRYSALIS — amivantamab 単剤 registrational
3. NEJM-2023-Zhou-Treatment outcomes and safety of mobocertinib in platinum-pretreated NSCLC with EGFR exon 20 insertions — Mobocertinib — competing exon 20 TKI (withdrawn)
4. LancetOncol-2024-Shu-Poziotinib in NSCLC with EGFR exon 20 insertions ZENITH20 — Poziotinib — exon 20 selective TKI
5. NEJM-2024-Cho-Amivantamab plus lazertinib in previously untreated EGFR-mutated advanced NSCLC MARIPOSA — MARIPOSA — amivantamab platform classic EGFR mutation

関連エンティティ

• Drugs: EGFR-MET-bispecific、Platinum-chemotherapy、Amivantamab
• Genes: EGFR、MET
• Concepts: EGFR-exon20-insertion
• Trials: MARIPOSA、DESTINY-Lung02

関連論文

Basic-Oncogene and genetics

• Hargreaves et al. NatGenet 2021 — Chromatin openness requires continuous SWISNF activity

Clinical-NSCLC-EGFR

• Passiglia et al. Cancer 2026 — Amivantamab in advanced non-small cell lung cancer with epidermal growth factor receptor exon 20 insertion mutations
• Kim et al. FrontOncol 2026 — Paired ctDNA analysis reveals diverse resistance mechanisms to mobocertinib in EGFR exon 20 insertion NSCLC
• Park et al. JClinOncol 2021 — Amivantamab in EGFR exon 20 insertion-mutated non-small-cell lung cancer progressing on platinum chemotherapy initial
• Zhou et al. NEnglJMed 2023 — Amivantamab plus chemotherapy in NSCLC with EGFR exon 20 insertions
• Zhou et al. NEnglJMed 2026 — First-line sunvozertinib in NSCLC with

Clinical-NSCLC-HER2

• Friedlaender et al. NatRevClinOncol 2022 — EGFR and HER2 exon 20 insertions in solid tumours from biology to treatment

合成 (Outputs)

• egfr-uncommon-mutation-treatment-selection