FDA Filing Accepted for Sunvozertinib in EGFR Exon 20 Insertion-Positive NSCLC
核心洞察
Dizal (搜索)'s sunvozertinib NDA has been submitted to the FDA for treating NSCLC (搜索) with EGFR (搜索) exon 20 insertion mutations after platinum-based chemotherapy.
The NDA submission is backed by phase 2 WU-KONG1 trial data, which demonstrated a 53.3% overall response rate in patients treated with sunvozertinib.
The median duration of response was not reached, with a 9-month duration of response rate of 57% observed in the study.
Dizal (搜索) has announced the FDA acceptance of its New Drug Application (NDA) for sunvozertinib (DZD9008) for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC (搜索)) harboring EGFR (搜索) exon 20 insertion mutations, whose disease has progressed on or after platinum-based chemotherapy. This submission is supported by data from the phase 2 WU-KONG1 trial, presented at the 2024 ASCO Annual Meeting, highlighting the potential of sunvozertinib as a targeted therapy in this challenging patient population.
Efficacy Data from WU-KONG1 Trial
The phase 2 WU-KONG1 trial (NCT03974022) evaluated the efficacy and safety of sunvozertinib in patients with NSCLC (搜索) harboring EGFR (搜索) exon 20 insertion mutations. The study enrolled patients who had previously been treated with platinum-based chemotherapy and had an ECOG performance status of 0 or 1. Patients treated with sunvozertinib at a 300-mg dose (n = 107) achieved a best overall response rate (ORR) of 53.3% (97.5% CI, 42.0%-64.3%) and a confirmed ORR of 44.9% (97.5% CI, 34.0%-56.1%). Complete response (CR) was observed in 2.8% of patients, with a confirmed CR rate of 1.9%. Partial response (PR) was seen in 50.5% of patients, with a confirmed PR rate of 43.0%. The median duration of response (DOR) was not reached, and the 9-month DOR rate was 57%.
Subgroup Analysis
Notably, the best ORRs for patients who received prior treatment with amivantamab-vmjw (Rybrevant) and those who did not were 50% and 53.8%, respectively, suggesting consistent activity regardless of prior amivantamab treatment.
Safety Profile
The safety profile of sunvozertinib was 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 Future Directions
"We are encouraged by the potential of sunvozertinib as a single oral agent to improve outcomes for patients with EGFR (搜索) exon 20 [insertion mutation–positive] NSCLC (搜索)," said Xiaolin Zhang, PhD, CEO of Dizal (搜索). The FDA's acceptance of the NDA marks a significant milestone for Dizal, representing its first NDA submission to the FDA. In August 2023, China’s National Medical Products Administration approved sunvozertinib for the treatment of adult patients with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations whose disease has progressed on or following platinum-based chemotherapy, based on data from the phase 2 WU-KONG6 trial (NCT05712902).