Sunvozertinib Approval Fills Treatment Gap in Pretreated EGFR Exon 20–Mutant NSCLC

Given the historical lack of approved oral tyrosine kinase inhibitors (TKIs) in EGFR exon 20–mutated metastatic non–small cell lung cancer (NSCLC), especially with the voluntary withdrawal of mobocertinib (Exkivity) for this indication in 2023,1 the FDA approval of sunvozertinib (Zegfrovy)2 provides a much-needed treatment option for patients with disease progression on or after platinum-based chemotherapy, according to Lyudmila A. Bazhenova, MD.

Findings from the phase 1/2 WU-KONG1 part B (WU-KONG1B) trial (NCT03974022) supported the agent’s accelerated approval on July 2, 2025. Among 85 patients in the primary efficacy population who received sunvozertinib at the recommended dose of 200 mg once daily, the overall response rate (ORR) was 46% (95% CI, 35%-57%) and the duration of response (DOR) was 11.1 months (95% CI, 8.2-not evaluable).2

“Currently, at least in the United States, the [phase 3] PAPILLON trial [NCT04538664] established carboplatin, pemetrexed, and amivantamab-vmjw [Rybrevant] as a standard first-line treatment option. Sunvozertinib can be used after [this regimen as] a second-line treatment option,” said Bazhenova, a clinical professor of medicine at the University of California San Diego (UCSD) and a medical oncologist at UCSD Moores Cancer Center.

In an interview with OncologyLive, Bazhenova outlined the clinical significance of the FDA approval of sunvozertinib for patients with NSCLC with EGFR exon 20 insertion mutations, reviewed key design elements and findings from the WU-KONG1B trial, and emphasized how this approval reinforces the therapeutic role of EGFR TKIs in this molecular subset.

OncologyLive: What is the significance of the FDA approval of sunvozertinib for this patient population?

Bazhenova: Sunvozertinib is an oral, irreversible, selective EGFR TKI. It technically targets both EGFR and HER2, but the development and approval is specific for patients with EGFR exon 20 insertion mutations. [The approval of this agent] adds another treatment option for patients with [NSCLC harboring] EGFR exon 20 insertions. [Prior to this approval], there were no approved TKIs for patients with EGFR exon 20 insertions. We used to have mobocertinib, which was an EGFR TKI, but it is no longer FDA approved [in the US]. Therefore, this treatment adds an oral, convenient treatment option for our patients [in the second line].

Please expand on the design and objectives of the WU-KONG1 study.

WU-KONG1B was a phase 2 global study evaluating the antitumor efficacy of sunvozertinib at 2 dose levels: 200 mg or 300 mg [daily]. [The study enrolled] patients who were pretreated with platinum[-based chemotherapy] and had EGFR exon 20 insertion [mutations]. Patients were treated with sunvozertinib once daily until discontinuation criteria were met.

During the randomization, patients were stratified by [the presence of] brain metastases at baseline and the number of prior systemic anticancer therapies. The primary end point for the study was ORR per RECIST 1.1 criteria by blinded independent review committee [assessment]. Secondary end points were pretty standard and included DOR and progression-free survival.

What key efficacy and safety findings from WU-KONG1 supported this regulatory decision?

WU-KONG1 enrolled 184 patients. [At a data cutoff of January 4, 2024], the ORR [in the primary analysis] was 54.3%. Confirmed complete response was achieved in 2.9% [of patients].3

Sunvozertinib is an EGFR TKI, so we expect the adverse effects [AEs] to be similar to [that of] other EGFR TKIs. In the WU-KONG1 trial, we saw [AEs such as] diarrhea, skin rash, and an increase in creatine phosphokinase. The majority of treatment-related AEs were grade 1 or 2.

How does this approval help open the door for similar agents to gain approval in the future?

We already have a proof of concept that EGFR TKIs are effective in the EGFR exon 20–mutated space, which was mobocertinib. Sunvozertinib kind of falls into the same pathway. The door was opened with mobocertinib, and this is just another option for [the same] patient population.

References

1. Takeda provides update on Exkivity (mobocertinib). News release. Takeda. October 2, 2023. Accessed July 16, 2025. https://www.takeda.com/newsroom/newsreleases/2023/ Takeda-Provides-Update-on-EXKIVITY-mobocertinib/
2. FDA grants accelerated approval to sunvozertinib for metastatic non-small cell lung cancer with EGFR exon 20 insertion mutations. FDA. Updated July 2, 2025. Accessed July 16, 2025. https://www.fda.gov/drugs/resources-information-approved- drugs/fda-grants-accelerated-approval-sunvozertinib-metastatic- non-small-cell-lung-cancer-egfr-exon-20
3. Yang JCH, Doucet L, Wang M, et al. A multinational pivotal study of sunvozertinib in platinum pretreated non-small cell lung cancer with EGFR exon 20 insertion mutations: primary analysis of WU-KONG1 study. J Clin Oncol. 2024;42(suppl 16):8513. doi:10.1200/JCO.2024.42.16_suppl.8513