Background
Pivotal phase 2 single-arm, open-label, multicentre (37 China sites); platinum-pretreated locally advanced/metastatic NSCLC with EGFR exon 20 insertion. N=104 enrolled (97 efficacy-evaluable); all had ≥1 prior systemic line including platinum. Sunvozertinib is an oral irreversible selective EGFR TKI active against exon 20 insertions.
Results
Interventions and follow up: Treatment: sunvozertinib 300 mg PO once daily.
Primary endpoint: confirmed ORR by independent review committee (two assessments ≥4 weeks apart).
mFollow up: 7.6mo (IQR 6.1–9.4).
Results: ORR: 61% (95% CI 50–71) among 97 evaluable (59/97 responders); all responses partial (no CR).
Subgroups: responses across age, sex, smoking, exon 20 insertion subtype, baseline brain metastasis, prior lines, and prior immunotherapy.
mDOR/mPFS: NR at this early cutoff.
Primary endpoint: confirmed ORR by independent review committee (two assessments ≥4 weeks apart).
mFollow up: 7.6mo (IQR 6.1–9.4).
Results: ORR: 61% (95% CI 50–71) among 97 evaluable (59/97 responders); all responses partial (no CR).
Subgroups: responses across age, sex, smoking, exon 20 insertion subtype, baseline brain metastasis, prior lines, and prior immunotherapy.
mDOR/mPFS: NR at this early cutoff.
Adverse events
Grade ≥3 (treatment-related): blood CK increased 17%, diarrhoea 8%, anaemia 6%.
Notable serious TRAEs: interstitial lung disease 5%, anaemia 3%, vomiting/nausea/pneumonia 2% each.
Notable serious TRAEs: interstitial lung disease 5%, anaemia 3%, vomiting/nausea/pneumonia 2% each.
Conclusions
Oral sunvozertinib produced clinically meaningful confirmed responses (ORR 61%) with manageable toxicity in platinum-pretreated EGFR exon 20 insertion NSCLC, supporting it as an oral targeted option for this difficult-to-treat subset.
Key Limitations
Single-arm, no comparator; short follow-up (median 7.6mo) leaves DOR/PFS immature; China-only enrollment limits generalisability.
Clinical Context
Supported the August 2023 conditional approval of sunvozertinib in China. The July 2025 US FDA accelerated approval (Zegfrovy) for platinum-pretreated EGFR exon 20 insertion advanced NSCLC was based primarily on the multinational WU-KONG1B study (not WU-KONG6), alongside a companion diagnostic; a randomised phase 3 vs platinum doublet is ongoing.