Dizal has announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for sunvozertinib (DZD9008) as a treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations. This application seeks to provide a new oral treatment option for patients whose disease has progressed following platinum-based chemotherapy.
The NDA is supported by data from part B of the phase 2 WU-KONG1 trial (NCT03974022), which were presented at the 2024 ASCO Annual Meeting. The trial evaluated sunvozertinib in patients with EGFR exon 20 insertion-positive NSCLC. Patients had to have disease progression on or after platinum-based chemotherapy and confirmed EGFR exon 20 insertion mutations detected by an FDA-approved test. The study's findings demonstrated promising efficacy and tolerability for sunvozertinib.
Efficacy Outcomes from WU-KONG1 Trial
The WU-KONG1 trial enrolled patients with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations confirmed by local or sponsor-designated laboratory testing. All patients had prior treatment with platinum-based chemotherapy and an ECOG performance status of 0 or 1. Initially, patients were randomized 1:1 to receive sunvozertinib at 200 mg per day or 300 mg per day. After an interim analysis, subsequent patients were enrolled to cohort 2 to receive the agent at 300 mg per day. Treatment continued until discontinuation criteria were met.
In the cohort treated with sunvozertinib at a 300-mg dose (n = 107), the best overall response rate (ORR) was 53.3% (97.5% CI, 42.0%-64.3%), with a confirmed ORR of 44.9% (97.5% CI, 34.0%-56.1%). The best responses included complete response (CR; 2.8%), confirmed CR (1.9%), partial response (PR; 50.5%), confirmed PR (43.0%), unconfirmed PR (3.7%), stable disease (36.4%), and progressive disease (7.5%). Response was not evaluable in 2.8% of patients. The median duration of response (DOR) was not reached, and the 9-month DOR rate was 57%. Notably, the respective best ORRs for patients who received prior treatment with amivantamab-vmjw (Rybrevant) and those who did not were 50% and 53.8%.
Safety Profile
Regarding safety, findings with sunvozertinib were consistent with previous studies. Treatment-related adverse effects (TRAEs) led to dose reductions in 36.0% of patients and treatment discontinuation in 6.3% of patients. Most TRAEs were grade 1 or 2, and no TRAEs led to death. The most common grade 3 or higher TRAEs reported in at least 2% of patients consisted of diarrhea (17.1%), increased blood creatine phosphokinase levels (10.8%), anemia (3.6%), rash (3.6%), increased lipase levels (3.6%), decreased neutrophil counts (2.7%), hypokalemia (2.7%), decreased appetite (2.7%), and asthenia (2.7%).
Regulatory Context and Next Steps
"We are encouraged by the potential of sunvozertinib as a single oral agent to improve outcomes for patients with EGFR exon 20 [insertion mutation–positive] NSCLC," said Xiaolin Zhang, PhD, chief executive officer of Dizal. "The filing for approval of sunvozertinib marks Dizal’s first NDA submission to the FDA, which represents an important step forward as we continue our efforts to address unmet medical needs globally. We look forward to working closely with the FDA on their review of our application."
Sunvozertinib received approval from China’s National Medical Products Administration in August 2023 for treating adult patients with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations after platinum-based chemotherapy, based on the phase 2 WU-KONG6 trial (NCT05712902).
