Sunvozertinib Proves Efficacy in EGFR-Mutant Non-Small Cell Lung Cancer

A phase 2 clinical study (NCT03974022)found that sunvozertinib (Zegfrovy) was efficacious in 2 different doses, but maintained a more favorable safety profile at the lower dose, in patients with platinum-pretreated, advanced non–small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations (exon20ins).¹

The WU-KONG1B study was an open-label, multicenter study meant to assess the safety, tolerability, pharmacokinetics, and antitumor efficacy of sunvozertinib. There was a total enrollment of 202 patients who were randomly assigned by 1:1 ratio to receive sunvozertinib 200mg (n = 91) or 300mg (n = 93) once daily. After an interim analysis, a third cohort enrolled and treated patients at 300 mg.

In July 2025, the FDA approved sunvozertinib in this patient population, supported by data from WU-KONG1B.²

What were the efficacy results?

Within the 200 mg randomized, 300 mg randomized, and 300 mg cohorts, there were 85, 89, and 107 patients who were efficacy evaluable.¹ The overall response rates (ORRs) were 45.9% (97.5% CI, 33.6%—58.5%), 47.2% (97.5% CI, 35.1%—59.5%), and 45.8% (97.5% CI, 34.8%—57.0%), respectively, per independent review committee (IRC) assessment. Between the 300 and 200 mg-randomized cohorts, higher ORRs were observed in patients with baseline brain metastasis (52.4% vs 28.6%) and previous amivantamab(Rybrevant) treatment (41.7% vs 25%), as well as a longer duration of response (DOR; 13.8 vs 11.1 months). 

“Sunvozertinib is one of the leading EGFR exon20ins inhibitors under clinical development and is the only approved EGFR TKI in China for the treatment of EGFR exon20ins NSCLC,” stated the authors of the study.¹“To address unmet medical needs for patients in other countries/regions outside of China, a multinational phase [2] dose-randomized study (WU-KONG1B) was conducted.”

What were the patient characteristics?

The baseline characteristics of patients between the 2 randomly assigned cohorts were well-balanced. Approximately 45% of patients were 65 or older. Over half of patients were female, had never smoked, and had an ECOG score of 1. Approximately two-thirds of patients were Asian, and the rest of the patients were predominantly White. Around 24% of patients had baseline brain metastases. There were more than 47 different EGFR exon20ins subtypes present among patients, including the major subtypes of 769_ASV and 770_SVD. All patients had been treated with platinum-based chemotherapy, more than 40% had been treated with onco-immunotherapy, and approximately 14% of patients were treated with amivantamab.² 

What were the primary and secondary endpoints?

The primary endpoint was blinded IRC-assessed confirmed ORR, and the secondary end point was DOR. Large variabilities of ORRs were observed in patients taking 200 mg once daily (>10% difference). Higher ORRs were observed in non-Asian patients who were taking 300 mg once daily compared with patients taking 200mg (43.3% vs 33.3%), in patients from non-Asian countries/regions (44.1% vs 33.3%), in patients with baseline brain metastases (52.4% vs 28.6%), and in patients who had previously received amivantamab treatment (41.7% vs 25%).^1,2

Among the 3 efficacy sets (200 mg randomized, 300 mg randomized, and 300 mg-all), median follow-ups were 17.6 months, 17.3 months, and 17 months. Overall survival (OS) rates were 62.1%, 73.7%, and 69.4%, respectively.²

The relative dose intensities at 200 mg and 300 mg once daily were 99.3% and 84.4%, respectively.

Treatment-related adverse events (TRAEs) grade ≥3 were reported in 40.7% and 58.6% of patients at the 200-mg- and 300-mg dose levels. The most common TRAEs grade ≥3 in the 200 and 300 mg cohorts included diarrhea (2.2% vs 18%), increased blood creatine phosphokinase (6.6% vs 12.6%), and anemia (4.4% vs 6.3%). Serious AEs were reported in 17.6% and 23.4% of patients, respectively. At 200 mg and 300 mg,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 patients, respectively. No TRAEs with fatal outcomes were reported.

What are the next steps in research?

A randomized phase 3 study (NCT05668988)² is currently being conducted to examine the results further through head-to-head comparison between sunvozertinib and platinum doublet chemotherapy in patients with treatment-naive advanced EGFR exon20ins NSCLC.

REFERENCES:

1. Yang J, 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 43, 3198-3208(2025).doi:10.1200/JCO-25-00788

2. 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 

3. A Study of DZD9008 Versus Platinum-Based Doublet Chemotherapy in Local Advanced or Metastatic Non-small Cell Lung Cancer (WU-KONG28). ClinicalTrials.gov. Updated September 30, 2025. Accessed October 16, 2025. https://www.clinicaltrials.gov/study/NCT05668988