Sunvozertinib Demonstrates PFS Benefit as First-Line Therapy in EGFR exon20ins NSCLC

Sunvozertinib (Zegfrovy) monotherapy met its primary end point of progression-free survival (PFS) in the phase 3 WU-KONG28 trial (NCT05668988), demonstrating a statistically significant and clinically meaningful improvement over platinum-based doublet chemotherapy as first-line treatment in patients with advanced non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations (exon20ins).¹

Sunvozertinib also showed superior results across all secondary end points, including confirmed objective response rate (cORR), duration of response (DOR), and disease control rate (DCR), and the agent was generally well tolerated with a safety profile consistent with prior studies. Full data are expected to be submitted for presentation at an upcoming international scientific congress.

"Finding a drug targeting EGFR [exon20ins] 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 Xiaolin Zhang, MD, CEO of Dizal, in a news release. "The success of this multinational pivotal study further validates [sunvozertinib’s] potential as first-line therapy for patients with EGFR exon20ins NSCLC.”

Trial Design and Drug Background

WU-KONG28 is a multinational, open-label, randomized, confirmatory phase 3 study evaluating sunvozertinib monotherapy vs platinum-based chemotherapy as first-line treatment in patients with advanced NSCLC with EGFR exon20ins. The study enrolled patients across 16 countries and regions in Asia, Europe, North America, and South America. The primary end point was PFS assessed by blinded independent central review.²

Sunvozertinib is an irreversible EGFR inhibitor that targets a broad spectrum of EGFR mutations with wild-type EGFR selectivity.

In July 2025, the FDA granted accelerated approval to the agent in this patient population, supported by efficacy data from the WU-KONG1B trial (NCT03974022).³ The major efficacy outcome measure evaluated in the WU-KONG1B trial was the cORR according to RECIST v1.1. The study reported an ORR of 46% (95% CI, 35%-57%). An additional key efficacy outcome measure was the DOR, which was 11.1 months (95% CI, 8.2-not evaluable).

Clinical Context and Unmet Need

EGFR exon20ins mutations present a distinct and historically difficult therapeutic challenge.¹ EGFR exon20ins is the third most frequent EGFR mutation, accounting for approximately 4% of all NSCLC and 12% of all EGFR-mutated NSCLC patients and represents a negative prognostic factor for survival. The mutations are structurally distinct from classical sensitizing EGFR alterations: unlike classical EGFR L858R point mutations or exon 19 deletions, which represent the majority of EGFR mutations in NSCLC, EGFR exon20ins mutations are associated with de novo resistance to targeted EGFR inhibitors and correlate with a poor patient prognosis.

The frequency of EGFR exon20ins mutations in NSCLC is estimated at 1% to 10%, and patients harboring these mutations exhibit a median overall survival of 16 months. Clinically, exon20ins mutations are associated with diagnosis at a significantly younger age, a higher proportion of never-smokers, and shorter relapse-free survival compared with other common EGFR mutations.

Until recently, platinum-based chemotherapy remained the standard of care in the first-line setting for this population, as conventional EGFR tyrosine kinase inhibitors have demonstrated minimal activity. Amivantamab (Rybrevant) in combination with platinum-based chemotherapy has shown improved first-line outcomes compared with chemotherapy alone, with a manageable safety profile, and has been considered a standard of care in this setting. WU-KONG28 now positions sunvozertinib as a potential chemotherapy-free oral monotherapy alternative in the first-line setting.

REFERENCES

1. Dizal announces positive topline phase 3 results from WU-KONG28 study: evaluating oral, once-daily ZEGFROVY® (sunvozertinib) vs. platinum-containing chemo doublet in first-line non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutation (exon20ins). News release. Dizal. March 23, 2025. Accessed March 23, 2026. https://tinyurl.com/hbxjj9xf

2. A study of DZD9008 versus platinum-based doublet chemotherapy in local advanced or metastatic non-small cell lung cancer (WU-KONG28). ClinicalTrials.gov. Updated February 17, 2026. Accessed March 23, 2026. https://clinicaltrials.gov/study/NCT05668988

3. FDA grants accelerated approval to sunvozertinib for metastatic non-small cell lung cancer with EGFR exon 20 insertion mutations. News release. US FDA. July 2, 2025. Accessed July 2, 2025. https://tinyurl.com/52k2z4z6