First-Line Treatment for Stage IV EGFR Exon 20 Insertion NSCLC
First-line therapy for Stage IV EGFR exon 20 insertion-positive non-small cell lung cancer (NSCLC) is a triplet regimen based on the PAPILLON (FDA-approved March 1, 2024) and PALOMA (FDA-approved December 18, 2025) clinical trials. This includes the bispecific antibody amivantamab (RYBREVANT) combined with chemotherapy (pemetrexed + carboplatin).
EGFR Tyrosine Kinase Inhibitors (TKIs) include sunvozertinib (FDA-approved July 2, 2025) and zipalertinib (PDUFA target date February 27, 2027), as well as firmonertinib and enozertinib. The antibody-drug conjugate datopotamab deruxtecan (Dato-DXd / DATROWAY) was FDA-approved June 23, 2025 for EGFR-mutated NSCLC after prior EGFR-targeted therapy and platinum chemotherapy.
The following list includes the latest clinical literature and conference presentations from 2025–2026, organized alphabetically by drug name.
For patient navigation and clinical trial matching, please contact the Exon 20 Group.
Amivantamab (RYBREVANT)
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Amivantamab-Chemotherapy in NSCLC with EGFR Exon 20 Insertions (Nov 2025)
Crossover-adjusted OS showed continued survival benefit (HR 0.52–0.60).
PubMed | Springer Full Text
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Patient-Reported Outcomes from PAPILLON (Oct 2025; print Mar 2026)
77% vs 60% free of symptomatic progression at 12 months; QoL maintained.
PubMed | Lung Cancer Journal
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Review: Biology to Amivantamab (Aug 2025)
Highlights 4 mechanisms: EGFR/MET blockade, ADCC, trogocytosis, receptor internalization.
PubMed
Enozertinib (ORIC-114)
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ESMO Asia 2025 Presentation
Phase 1b shows systemic and CNS activity; well tolerated.
Press Release
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Discovery & Development (Cancer Research, Nov 2025)
Brain-penetrant, selective irreversible inhibitor.
View Publication
Firmonertinib / Furmonertinib
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FURTHER Trial Final Analysis (Sep 2025)
1L: median PFS 16 months; ORR 68.2%; CNS responses observed.
Press Release
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FURVENT Phase 3 (Projected mid-2026)
Global pivotal trial in 1L EGFR exon 20 NSCLC.
Company Update
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FURMO-003 Phase 2 (WCLC 2025)
Topline efficacy in pretreated patients.
Abstract
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Case Report (Jan 2026)
27-month PFS with high-dose therapy; mild toxicity.
PMC
Sunvozertinib (ZEGFROVY)
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OncologyLive Review (Apr 2026)
Discusses evolving TKI landscape and NDA timelines.
Read Article
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WU-KONG1B Study (JCO, Sep 2025)
Clinically meaningful ORR with manageable safety.
PubMed | JCO
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FDA Approval Editorial (Nov 2025)
Positions sunvozertinib post-platinum ± amivantamab.
Wiley
Zipalertinib (CLN-081 / TAS6417)
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NDA Accepted by FDA (Apr 2026)
For EGFR exon 20 NSCLC post-platinum therapy; PDUFA Feb 27, 2027.
Targeted Oncology | BioSpace
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Clinical Overview (Jan 2026)
REZILIENT trials and combination strategies.
PMC | MDPI
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REZILIENT1 Trial (JCO 2025)
ORR 35.2%, median DOR 8.8 months.
JCO Full Text