Sunvozertinib Monotherapy Bests Platinum-Doublet Chemotherapy in EGFR Exon 20+ NSCLC

Sunvozertinib (Zegfrovy) led to a significant improvement in progression-free survival (PFS) vs platinum-based doublet chemotherapy as first-line therapy in patients with advanced non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertions, meeting the primary end point of the multinational, confirmatory phase 3 WU-KONG28 trial (NCT05668988).¹

Findings from the primary analysis will be submitted for presentation at a forthcoming global meeting, and data will be discussed with regulatory agencies with respect to potential new drug applications for the agent.

“Finding a drug targeting EGFR exon 20 insertion mutations is especially challenging due to their enormous heterogeneity. We have identified over 100 different subtypes of EGFR exon 20 [insertions] 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,” Xiaolin Zhang, PhD, chief executive officer of Dizal and adjunct professor at Peking University in Beijing, China, said in a news release.

“The success of this multinational pivotal study further validates [sunvozertinib’s] potential as first-line therapy for patients with EGFR exon 20 insertion[–positive] NSCLC. We extend our sincere gratitude to the patients, their families, and the investigators worldwide for their dedication and contribution to this study. We look forward to sharing comprehensive data with the global scientific community,” Zhang added.

What is the development history of sunvozertinib in NSCLC?

In July 2025, the FDA granted accelerated approval to sunvozertinib for the treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations with disease progression on or after platinum-based chemotherapy.² The designation was based on efficacy findings from the phase 2 WU-KONG1B trial (NCT03974022), showcasing an overall response rate of 46% (95% CI, 35%-57%) in patients who received the agent at 200 mg orally, once daily (n = 85).

The agent also earned breakthrough therapy designation (BTD) in the first-line setting for the same population based on findings from WU-KONG1B.³ In China, sunvozertinib also holds an indication in the pretreated setting as well as BTD in the first-line setting in China.¹

How was the WU-KONG28 trial designed?

WU-KONG28 is a multinational, open-label, randomized, confirmatory phase 3 trial comparing the efficacy and safety of sunvozertinib with platinum-based chemotherapy as first-line treatment for patients with advanced NSCLC harboring EGFR exon 20 insertions.¹ The study enrolled patients across 16 countries and regions in Asia, Europe, North America, and South America.

In addition to the primary end point of blinded independent central review–assessed PFS per RECIST 1.1, the key secondary end point was overall survival.⁴

Patients who were at least 18 years old and had received a histologically or cytologically confirmed diagnosis of stage IIIB, IIIC, or IV nonsquamous NSCLC not eligible for curative therapy were recruited for enrollment. Additional eligibility criteria stipulated the availability of sufficient tumor tissue for confirmation of an EGFR exon 20 insertion mutation; adequate organ and hematologic function, an ECOG performance status of 0 or 1, life expectancy of at least 12 weeks, and at least 1 measurable lesion per RECIST 1.1 criteria.

Patients with prior treatment, spinal cord compression or leptomeningeal metastasis, concurrent EGFR mutations, history of stroke or intracranial hemorrhage within 6 months before randomization, or evidence of severe or uncontrolled systemic diseases were excluded.

Eligible patients received 300 mg of oral sunvozertinib once daily until discontinuation criteria were met, or up to 6 cycles of 500 mg/m² of pemetrexed plus intravenous carboplatin at an area under the plasma concentration time curve of 5 mg/mL per minute, every 3 weeks. Patients whose disease had not progressed as of the fourth cycle of therapy could receive pemetrexed maintenance until discontinuation criteria were met.

What is the overall significance of these positive topline findings?

“The positive topline results from WU-KONG28 study represent an important advancement for treating patients with EGFR exon 20 insertion[–positive] NSCLC,” Caicun Zhou, MD, PhD, principal investigator of the study, president of the International Association for the Study of Lung Cancer, and director of Oncology at Shanghai East Hospital in China, said in a news release.¹

“[Sunvozertinib] is currently the only single-agent, small-molecule targeted therapy approved in both China and the United States for patients with EGFR exon 20 insertion[–positive] NSCLC. In this phase 3 trial, first-line treatment with [sunvozertinib] significantly prolonged PFS compared to platinum-based doublet chemotherapy. These results suggest that [sunvozertinib] may offer an effective and convenient treatment option for treatment-naive patients with EGFR exon 20 insertion[–positive] NSCLC,” Zhou said.

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). Dizal. News release. March 21, 2026. Accessed March 23, 2026. https://www.dizalpharma.com/news/detail?id=109&search=&currentPage=1
2. FDA grants accelerated approval to sunvozertinib for metastatic non-small cell lung cancer with EGFR exon 20 insertion mutations. FDA. July 2, 2025. Accessed March 23, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sunvozertinib-metastatic-non-small-cell-lung-cancer-egfr-exon-20
3. FDA grants breakthrough therapy designation to sunvozertinib for the first-line treatment of patients with advanced non-small cell lung cancer harboring EGFR exon 20 insertion mutations. News release. Dizal. April 7, 2024. Accessed March 23, 2026. https://www.dizalpharma.com/news/detail?id=70
4. 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