Sunvozertinib NDA Submitted to FDA for EGFR Exon 20+ NSCLC

Dizal (搜索)搜索该词条 has announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for sunvozertinib查看药品详情 (DZD9008) as a treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC (搜索)搜索该疾病) harboring EGFR (搜索)搜索该靶点 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查看临床试验), which were presented at the 2024 ASCO Annual Meeting. The trial evaluated sunvozertinib查看药品详情 in patients with EGFR (搜索)搜索该靶点 exon 20 insertion-positive NSCLC (搜索)搜索该疾病. 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 (搜索)搜索该疾病 harboring EGFR (搜索)搜索该靶点 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查看药品详情 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查看药品详情 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查看药品详情 (Rybrevant) and those who did not were 50% and 53.8%.

Safety Profile

Regarding safety, findings with sunvozertinib查看药品详情 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查看药品详情 as a single oral agent to improve outcomes for patients with EGFR (搜索)搜索该靶点 exon 20 [insertion mutation–positive] NSCLC (搜索)搜索该疾病," said Xiaolin Zhang, PhD, chief executive officer of Dizal (搜索)搜索该词条. "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查看药品详情 received approval from China’s National Medical Products Administration in August 2023 for treating adult patients with locally advanced or metastatic NSCLC (搜索)搜索该疾病 harboring EGFR (搜索)搜索该靶点 exon 20 insertion mutations after platinum-based chemotherapy, based on the phase 2 WU-KONG6 trial (NCT05712902查看临床试验).