China CDE Grants Breakthrough Therapy Status to Sunvozertinib for First-Line Treatment of EGFR Exon 20 NSCLC

Dizal, a biopharmaceutical firm recognized for its innovative contributions to cancer and immunological treatments, has announced that China’s National Medical Products Administration (NMPA) has awarded Breakthrough Therapy Designation (BTD) to their drug, sunvozertinib. This designation is for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that exhibit the epidermal growth factor receptor (EGFR) exon 20 insertion mutations (exon20ins) who have not previously undergone systemic therapies.

This recent BTD marks the fourth such designation for sunvozertinib in the context of EGFR exon20ins NSCLC. Earlier this year, the U.S. Food and Drug Administration (FDA) granted a similar BTD for the drug in the first-line setting. The FDA and China CDE have previously approved sunvozertinib for relapsed or refractory patients.

The BTD processes in the U.S. and China aim to accelerate the development and review of new drugs that show significant improvement over existing treatments for serious or life-threatening conditions. Drugs with BTD can be considered for priority review during the New Drug Application (NDA) phase.

Xiaolin Zhang, PhD, CEO of Dizal, emphasized the significance of obtaining four BTDs from both the U.S. and Chinese regulatory bodies. He stated, “This underscores sunvozertinib’s potential and our dedication to bringing innovative treatments to patients worldwide. Sunvozertinib is the first and only oral drug approved for treating lung cancer patients with EGFR exon20ins. We are committed to speeding up clinical trials and regulatory submissions to provide this new treatment option to more patients.”

The new BTD was awarded based on data from the global multi-center phase I/II study (WU-KONG1) and phase II study (WU-KONG15) which focused on Chinese patients. These studies indicated that sunvozertinib, as a single oral agent, achieved a confirmed objective response rate (cORR) of 78.6% and a median progression-free survival (mPFS) of 12.4 months in treatment-naïve patients with advanced or metastatic NSCLC with EGFR exon20ins. The drug was well tolerated, with a safety profile similar to traditional EGFR-TKIs.

Sunvozertinib is currently under evaluation in the WU-KONG28 study, a phase III, multinational, randomized trial comparing it with platinum doublet chemotherapies in treatment-naive patients globally. NSCLC with EGFR exon20ins is challenging to treat due to its unique spatial configuration, diverse mutation subtypes, and high heterogeneity. In some regions, platinum-based chemotherapies are the only first-line treatment available.

In 2023, China approved sunvozertinib for treating relapsed or refractory NSCLC with EGFR exon20ins, based on the WU-KONG6 study results. Dizal presented findings from the WU-KONG1 Part B study, a multinational study involving patients from Asia, Europe, North America, and South America, at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. The study met its primary endpoint, and regulatory submissions for market approval are ongoing.

Sunvozertinib is an irreversible EGFR inhibitor designed by Dizal scientists to target a broad range of EGFR mutations with selectivity for wild-type EGFR. It received approval in August 2023 from NMPA to treat advanced NSCLC with EGFR exon20ins after platinum-based chemotherapies. The WU-KONG6 study showed a confirmed overall response rate (cORR) of 60.8% as assessed by the Independent Review Committee (IRC). The drug showed efficacy across various EGFR exon20ins subtypes and in patients with pretreated and stable brain metastasis. It also demonstrated promising anti-tumor activity in NSCLC patients with EGFR sensitizing, T790M, and uncommon mutations, as well as HER2 exon20ins.

Sunvozertinib exhibited a well-tolerated and manageable safety profile in clinical trials. The most common treatment-emergent adverse events (TEAEs) were of Grade 1/2 and clinically manageable. Two global pivotal studies, WU-KONG1 Part B and WU-KONG28, are ongoing in the second-line and first-line settings respectively, for NSCLC patients with EGFR exon20ins.

Dizal is committed to discovering and developing innovative treatments for cancer and immunological diseases, with the aim of addressing unmet medical needs worldwide. The company has established a competitive portfolio, with two leading assets in global pivotal studies that have already been launched in China.