Sunvozertinib Exhibits Favorable Responses in EGFR-Mutated NSCLC

Sunvozertinib (Zegfrovy) exhibited robust confirmed objective response rates (ORRs) among patients with non–small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations following treatment with platinum-based chemotherapy, according to results from the phase 2 WU-KONG1B trial (NCT03974022) published in the Journal of Clinical Oncology.¹

Among patients who received 200 mg (n = 85) or 300 mg of sunvozertinib (n = 107), the confirmed ORRs were 45.9% (97.5% CI, 33.6%-58.5%) and 45.8% (97.5% CI, 34.8%-57.0%) per independent review committee (IRC) assessment, significantly rejecting the null hypothesis (P < .0001). Additionally, the disease control rate (DCR) was 89.4% (97.5% CI, 79.6%-95.6%) and 88.8% (97.5% CI, 80.1%-94.6%) in the respective arms. In the 200 mg and 300 mg cohorts, 5.9% vs 2.8% attained a complete response, 40.0% vs 43.0% had a partial response, and 43.5% vs 43.0% experienced stable disease.

Furthermore, tumor responses were observed in both arms, regardless of variables, with larger variabilities in response observed at 200 mg once daily. Subgroup analysis revealed higher confirmed ORRs at 300 mg once daily vs 200 mg once daily in patients who are not Asian (43.3% vs 33.3%) or from non-Asian regions (44.1% vs 33.3%), in those with brain-metastatic disease (52.4% vs 28.6%), and in those who previously received amivantamab-vmjw (Rybrevant) treatment (41.7% vs 25%).

Additionally, the median duration of responses (DORs) in the 200 and 300 mg arms were 11.1 months (95% CI, 8.2-not evaluable [NE]) vs 9.8 months (95% CI, 8.3-13.9). Moreover, the estimated median progression-free survival (PFS) was 8.4 months and 6.9 months, with median follow-ups of 15.2 months and 15.0 months, respectively. Furthermore, the respective 12-month overall survival (OS) rates were 62.1% vs 69.4%.

“Based on its favorable benefit/risk profile, sunvozertinib has the potential to address the unmet medical needs of pretreated NSCLC with EGFR [exon 20 insertion mutations]. [The randomized phase 3 WU-KONG28 trial (NCT05668988)] is ongoing to further validate the results through head-to-head comparison between sunvozertinib and platinum-doublet chemotherapy in patients with treatment-naïve advanced [NSCLC with] EGFR [exon 20 insertion mutations],” lead study author James Chih-Hsin Yang, MD, PhD, director of the Graduate Institute of Oncology and the Department of Oncology at the National Taiwan University Hospital, wrote in the publications with study coinvestigators.¹

The multinational phase 2 study enrolled patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. Those with an ECOG performance status of 0 to 1 and stable, irradiated brain metastases were permitted. Initially, patients were randomly assigned to receive 200 mg (n = 91) or 300 mg (n = 93) of sunvozertinib. After an interim analysis, 18 additional patients were enrolled to the 300 mg cohort, bringing the total up to 111 patients.

Treatment beyond disease progression was permitted if investigators assessed that a patient was still deriving clinical benefit. Adverse effects (AEs) were coded per Medical Dictionary for Regulatory Activities Terminology v27.0 and graded per National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. Additionally, in the event of grade 3 or higher treatment-related AEs (TRAEs), dose interruption or reduction was employed.

The primary end point was confirmed ORR per IRC assessment. The key secondary end point was DOR per IRC assessment. Other secondary end points included investigator-assessed confirmed ORR and DOR, as well as PFS, OS, and safety.

TRAEs at a grade of 3 or higher occurred in 40.7% and 58.6% of patients in the 200 mg and 300 mg cohorts, respectively. Serious AEs in each arm were reported in 17.6% vs 23.4%, and TRAEs leading to dose interruption, reduction, and discontinuation occurred in 35.2% vs 49.5%, 23.1% vs 38.7%, and 4.4% vs 7.2% of each cohort. Additionally, no patients in either arm had died due to TRAEs.

The phase 3 WU-KONG28 trial will randomly assign patients 1:1 to receive sunvozertinib or platinum-based chemotherapy composed of pemetrexed and carboplatin.² Eligible patients will have advanced or metastatic NSCLC with EGFR exon 20 insertion mutations who are either newly diagnosed or who have not received prior systemic therapy for advanced-stage disease. The primary end point will be blinded independent committee review-assessed PFS per RECIST v1.1 criteria.

References

1. Yang JC, Wang M, Doucet L, et al. Phase II dose-randomized study of sunvozertinib in platinum-pretreated non–small cell lung cancer with epidermal growth factor receptor exon 20 insertion mutations (WU-KONG1B). J Clin Oncol. Published online September 9, 2025. doi:10.1200/JCO-25-00788
2. A study of DZD9008 versus platinum-based doublet chemotherapy in local advanced or metastatic non-small cell lung cancer (WU-KONG28).