As reported at the 2026 ASCO Annual Meeting and in The New England Journal of Medicine by Zhou et al, the phase III WU-KONG28 trial has shown that first-line sunvozertinib improved progression-free survival vs chemotherapy in patients with advanced nonsquamous non–small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations.
Study Details
In the international open-label trial (63% of patients were Asian), 324 patients were randomly assigned between December 2022 and May 2025 to receive sunvozertinib at 300 mg once daily (n = 163) or chemotherapy (n = 161); chemotherapy consisted of carboplatin AUC = 5 and pemetrexed at 500 mg/m2 every 3 weeks for up to four or six cycles (at investigator discretion), followed by pemetrexed maintenance therapy. Treatment continued until disease progression or other discontinuation criteria were met. Crossover to sunvozertinib treatment was permitted after confirmed disease progression. The primary endpoint was progression-free survival on blinded independent central review.
Key Findings
With a median follow-up of 24.0 months (95% confidence interval [CI] = 20.8–26.5 months) in the sunvozertinib group and 18.0 months (95% CI = 13.1–26.0 months) in the chemotherapy group, median progression-free survival was 10.3 months (95% CI = 8.3–14.0 months) in the sunvozertinib group vs 7.5 months (95% CI = 6.7–8.5 months) in the chemotherapy group (hazard ratio [HR] = 0.65, 95% CI = 0.50–0.85, P < .001). Rates at 12 and 18 months were 46.1% vs 26.7% and 33.2% vs 17.1%.
Data for overall survival were immature (38.9% maturity). A total of 101 (90.2%) of 112 patients in the chemotherapy group crossed over to receive sunvozertinib after disease progression. Objective response rates were 58.9% in the sunvozertinib group vs 31.1% in the chemotherapy group; median duration of response was 11.2 vs 7.1 months.
Grade 3 or higher adverse events were reported in 75.5% of the sunvozertinib group and 56.7% of the chemotherapy group; the most common included increased serum creatine kinase levels (20.9%), diarrhea (14.1%), and anemia (9.2%) in the sunvozertinib group and decreased neutrophil count (18.7%) and anemia (11.3%) in the chemotherapy group (prior to crossover to sunvozertinib). Serious adverse events were reported in 45.4% vs 26.7% of patients. Death considered related to treatment occurred in one patient in the chemotherapy group (due to pneumonia).
The investigators concluded: “The efficacy of sunvozertinib was superior to that of chemotherapy as first-line treatment for advanced NSCLC with EGFR exon 20 insertions.”
Caicun Zhou, MD, PhD, of Shanghai East Hospital, Shanghai, China, is the corresponding author for the New England Journal of Medicine article.
DISCLOSURE: The study was funded by Dizal Pharmaceuticals. For full disclosures of the study authors, visit nejm.org.
