Dizal Pharmaceuticals' sunvozertinib, an oral epidermal growth factor receptor (EGFR) inhibitor, has received Breakthrough Therapy Designation (BTD) from the U.S. Food and Drug Administration (FDA) for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations. This regulatory decision aims to expedite the development and review of sunvozertinib, offering a potential new treatment option for a subset of NSCLC patients with limited effective therapies. The BTD is based on promising results from the global, multi-center Phase I/II WU-KONG1 study.
Clinical Efficacy and Safety
The FDA's decision was influenced by data presented at the 2023 European Society for Medical Oncology (ESMO) Congress, where sunvozertinib demonstrated a confirmed objective response rate (cORR) of 78.6% and a median progression-free survival (mPFS) of 12.4 months in first-line treatment. These results were observed in patients treated with a 300-mg dose of sunvozertinib (n = 9) within the WU-KONG1 trial. The study's findings suggest a clinically meaningful benefit for patients with EGFR exon 20 insertion mutations, which are present in approximately 2% to 4% of NSCLC cases and are often resistant to standard EGFR tyrosine kinase inhibitors (TKIs).
In terms of safety, the most common grade 3 or greater treatment-emergent adverse events (TEAEs) included increased blood creatine phosphokinase (17.5%), diarrhea (7%), and increased lipase (5.3%). These adverse events were generally manageable and reversible, with a small number of patients requiring dose reductions or discontinuations.
Mechanism of Action and Prior Approvals
Sunvozertinib (DZD9008) is designed to selectively target a wide spectrum of EGFR mutations, including exon 20 insertions, while sparing wild-type EGFR. This selectivity aims to improve efficacy and reduce off-target toxicities. The drug has already received BTDs from both the FDA and China's Center for Drug Evaluation (CDE) for relapsed or refractory NSCLC patients. In 2023, sunvozertinib was approved in China for patients who had progressed following first-line treatment.
Ongoing Clinical Trials and Future Directions
Currently, Dizal is conducting a randomized global Phase III study (WU-KONG28) in the first-line setting to further evaluate sunvozertinib's efficacy and safety. Enrollment for the global pivotal study in the relapsed and refractory setting (WU-KONG1 PART B) has been completed, with results expected to be presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. New Drug Application (NDA) submissions for approvals in the United States and European Union for the relapsed/refractory setting are anticipated later in 2024.
Expert Commentary
"We are delighted with the FDA’s decision granting the Breakthrough Therapy Designation to sunvozertinib for first-line treatment... Multiple clinical trials have consistently demonstrated sunvozertinib’s significant clinical benefits to our patients. As a single, oral agent, it offers apparent advantages in both safety and patient compliance over chemotherapies and infusion," said Xiaolin Zhang, PhD, CEO of Dizal.
