Background
Phase 3, international, open-label RCT; N=324; treatment-naïve advanced nonsquamous NSCLC with EGFR exon 20 insertion mutations; randomized 1:1; crossover to sunvozertinib permitted after confirmed progression.
Results
Interventions and follow up: Arm A: Sunvozertinib, oral, once daily (n=163)
Arm B: Chemotherapy — carboplatin + pemetrexed (n=161)
Primary endpoint: PFS by blinded independent central review (BICR)
Secondary endpoints: OS, investigator-assessed PFS, ORR, change in tumor size, DoR
mFollow up: NR (OS 38.9% mature)
Results: PFS (BICR): 10.3 vs 7.5 mo; HR 0.65 (95% CI 0.50–0.85); P<.001
12-mo PFS: 46.1% vs 26.7%
ORR: 58.9% vs 31.1%
Median best change in tumor size: −42.1% vs −24.7%
DoR: 11.2 vs 7.1 mo
OS: NR (immature, 38.9% maturity)
Arm B: Chemotherapy — carboplatin + pemetrexed (n=161)
Primary endpoint: PFS by blinded independent central review (BICR)
Secondary endpoints: OS, investigator-assessed PFS, ORR, change in tumor size, DoR
mFollow up: NR (OS 38.9% mature)
Results: PFS (BICR): 10.3 vs 7.5 mo; HR 0.65 (95% CI 0.50–0.85); P<.001
12-mo PFS: 46.1% vs 26.7%
ORR: 58.9% vs 31.1%
Median best change in tumor size: −42.1% vs −24.7%
DoR: 11.2 vs 7.1 mo
OS: NR (immature, 38.9% maturity)
Adverse events
Grade ≥3 (any): 75.5% vs 56.7%
Most common grade ≥3 (sunvozertinib): increased creatine kinase, diarrhea, anemia
Treatment-related deaths: none attributed to sunvozertinib
Most common grade ≥3 (sunvozertinib): increased creatine kinase, diarrhea, anemia
Treatment-related deaths: none attributed to sunvozertinib
Conclusions
First-line sunvozertinib, an oral EGFR exon20ins-active TKI, significantly improved PFS, ORR and DoR vs platinum-doublet chemotherapy in advanced EGFR exon20ins NSCLC, with OS immature. Establishes a chemotherapy-free oral targeted option in the frontline setting, where the drug previously held accelerated approval only after platinum.
Key Limitations
OS immature (38.9% maturity) and crossover permitted, which may attenuate any future OS difference; open-label design (PFS by BICR mitigates bias); higher grade ≥3 toxicity (CK elevation, diarrhea, anemia); no head-to-head vs amivantamab-based 1L regimens (PAPILLON).
Clinical Context
Sunvozertinib (ZEGFROVY, Dizal) holds FDA accelerated approval (2025) for EGFR exon20ins NSCLC after platinum chemotherapy (approved at 200 mg PO once daily); WU-KONG28 is the confirmatory first-line phase 3. An sNDA is under FDA review and the NMPA granted priority review for first-line use. Prior 1L standard for exon20ins was amivantamab + chemotherapy (PAPILLON); WU-KONG28 offers an oral, chemo-free targeted alternative. Presented at ASCO 2026 and simultaneously published in NEJM.