ZEGFROVY Achieves Primary Endpoint in Phase 3 Trial for First-Line EGFR Exon 20 Insertion NSCLC
Key Insights
Dizal (search)'s WU-KONG28 Phase 3 study demonstrated that ZEGFROVY (search) (sunvozertinib) significantly improved progression-free survival compared to platinum-based chemotherapy in first-line EGFR (search) exon 20 insertion NSCLC (search) patients.
The multinational trial represents the first Phase 3 study to show meaningful benefits with an oral, once-daily, chemotherapy-free targeted therapy for this challenging mutation subset.
ZEGFROVY (search) showed superior results across all secondary endpoints including objective response rate, duration of response, and disease control rate while maintaining a well-tolerated safety profile.
Dizal (search) announced positive topline results from its multinational Phase 3 WU-KONG28 study, demonstrating that ZEGFROVY (search) (sunvozertinib) monotherapy significantly improved progression-free survival compared to platinum-based doublet chemotherapy as first-line treatment in advanced non-small cell lung cancer (NSCLC (search)) patients with EGFR (search) exon 20 insertion mutations (exon20ins). The findings suggest ZEGFROVY monotherapy has the potential to become the first and only chemotherapy-free, oral agent to treat newly diagnosed NSCLC patients with EGFR exon20ins.
Study Design and Results
WU-KONG28 is a multinational, open-label, randomized confirmatory Phase 3 study that enrolled patients across 16 countries and regions in Asia, Europe, North America and South America. The study evaluated ZEGFROVY (search) versus platinum-based chemotherapy as first-line treatment in advanced NSCLC (search) patients with EGFR (search) exon20ins, with progression-free survival assessed by blinded independent central review as the primary endpoint.
The study met its primary endpoint, with topline results demonstrating that ZEGFROVY (search) significantly improved PFS compared to platinum-based doublet chemotherapy with meaningful clinical benefit. Beyond the primary endpoint, ZEGFROVY also showed superior results in all secondary endpoints, including confirmed objective response rate (cORR), duration of response (DOR), and disease control rate (DCR), compared to platinum-based chemotherapy doublet.
Clinical Significance
"Finding a drug targeting EGFR (search) exon 20 insertion mutations is especially challenging due to their enormous heterogeneity. We have identified over 100 different subtypes of EGFR exon20ins clinically. Despite tremendous efforts, there is no success yet in finding an effective target drug that can spare patients from chemotherapies. WU-KONG28 study has the potential to change all that," said Dr. Xiaolin Zhang, CEO of Dizal (search).
Prof. Caicun Zhou, MD, PhD of Shanghai East Hospital (search) and the principal investigator of the study, emphasized the clinical importance: "ZEGFROVY (search) is currently the only single-agent, small-molecule targeted therapy approved in both China and the United States for patients with EGFR (search) exon 20 insertion NSCLC (search). In this Phase 3 trial, first-line treatment with ZEGFROVY significantly prolonged PFS compared to platinum-based doublet chemotherapy. These results suggest that ZEGFROVY may offer an effective and convenient treatment option for treatment-naïve patients with EGFR exon20ins NSCLC."
Safety Profile
ZEGFROVY (search) was generally well tolerated with a safety profile consistent with previous studies. The most common drug-related treatment-emergent adverse events were Grade 1/2 in nature and clinically manageable, maintaining the well-tolerated and manageable safety profile demonstrated in previous clinical studies.
Regulatory Status and Next Steps
ZEGFROVY (search) was previously approved in both China and the U.S. for the treatment of relapsed or refractory NSCLC (search) with EGFR (search) exon20ins. In the first-line setting, ZEGFROVY has been granted Breakthrough Therapy Designations by both the U.S. Food and Drug Administration (search) (FDA) and China Center for Drug Evaluation (search) (CDE). Based on WU-KONG28 study results, Dizal (search) plans to engage with regulatory authorities regarding potential new drug applications.
About ZEGFROVY
ZEGFROVY (search) is an irreversible EGFR (search) inhibitor discovered by Dizal (search) scientists targeting a wide spectrum of EGFR mutations with wild-type EGFR selectivity. The drug is currently approved in the U.S. and China for the treatment of adult patients with locally advanced or metastatic NSCLC (search) with EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy.
In addition to EGFR (search) exon20ins, ZEGFROVY (search) has demonstrated encouraging anti-tumor activity in NSCLC (search) patients with EGFR sensitizing, T790M, and uncommon mutations, as well as HER2 (search) exon20ins. Pre-clinical and clinical results of ZEGFROVY have been published in peer-reviewed journals including Cancer Discovery, The Lancet Respiratory Medicine and Journal of Clinical Oncology.
Detailed data from the primary analysis will be submitted for presentation at an upcoming international scientific congress.