Sunvozertinib monotherapy versus platinum-based chemotherapy as first-line treatment for advanced NSCLC with EGFR exon20ins: Primary analysis of a multinational phase 3 randomized study (WU-KONG28).

LBA8500 Background: Sunvozertinib has been granted accelerated approval in the US and China for the treatment of patients with advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor exon 20 insertion mutations (EGFR exon20ins) who failed platinum-based chemotherapy, based on results from two phase 2 single arm pivotal studies (WU-KONG1B [NCT03974022] and WU-KONG6 [NCT05712902]). WU-KONG28 (NCT05668988) is a multinational randomized confirmatory phase 3 study to compare sunvozertinib versus platinum-based chemotherapy as first-line treatment in advanced NSCLC patients with EGFR exon20ins. Here we reported the primary analysis of WU-KONG28 study results. Methods: Eligible patients were randomized in a 1:1 ratio, stratified by baseline brain metastasis status, to receive either sunvozertinib 300 mg once daily or chemotherapy (carboplatin [AUC5] and pemetrexed [500 mg/m²]) once every 3 weeks for up to 6 cycles, followed by pemetrexed maintenance therapy until disease progression or other discontinuation criteria were met. Patients in the chemotherapy arm could cross over to receive sunvozertinib upon confirmed progressive disease by the blinded independent central review (BICR). The primary endpoint was progression free survival (PFS) assessed by BICR per RECIST 1.1. Secondary endpoints included overall survival (OS), objective response rate (ORR), duration of response (DoR), and safety profile. PFS and OS were analyzed using log-rank test and Cox proportional hazards model. The data cutoff date was Jan 16, 2026. Results: A total of 324 patients were randomized to receive sunvozertinib (N=163) or chemotherapy (N=161). Baseline characteristics were generally balanced between the two arms. PFS by BICR was significantly longer with sunvozertinib than chemotherapy (median: 10.3 vs 7.5 months; hazard ratio [HR]: 0.65, 95% confidence interval [CI]: 0.50, 0.85, p=0.0008). The PFS benefit was consistent in trends across subgroups. In the chemotherapy arm, 90.2% of patients with BICR-confirmed disease progression crossed over to receive sunvozertinib. The OS data were immature. Patients in the sunvozertinib arm showed higher confirmed ORR (58.9% vs 31.1%) and longer median DoR (11.2 vs 7.1 months). Safety profile of sunvozertinib was similar to what was previously reported. Drug-related treatment emergent adverse events (TEAEs) leading to treatment discontinuation occurred in 7.4% of patients. No drug-related TEAE leading to fatal outcome was reported. Conclusion: Sunvozertinib demonstrated significantly superior antitumor efficacy than chemotherapy with a manageable safety profile. These results support sunvozertinib as a first-line treatment for advanced NSCLC harboring EGFR exon20ins. Clinical trial information: NCT05668988 .