Dizal Reveals New Findings from Biomarker Analysis, Highlighting Sunvozertinib as an Effective Treatment for Non-small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations

• Antitumor efficacy of sunvozertinib was observed in patients regardless of baseline EGFR exon20ins status in plasma ctDNA.
• Sunvozertinib could effectively clear EGFR exon20ins in plasma ctDNA, confirming its direct effect on EGFR pathway.
• The resistance to sunvozertinib could be through EGFR-dependent and EGFR-independent mechanisms and combination of golidocitinib, a JAK1 inhibitor, with chemotherapy could be a potential approach to overcome sunvozertinib resistance.

SHANGHAI, May 24, 2024 /PRNewswire/ -- Dizal (SSE:688192), a biopharmaceutical company committed to developing groundbreaking new medicines for the treatment of cancer and immunological diseases, announced new findings from a biomarker study in non-small cell lung cancer (NSCLC) patients with exon 20 insertion (exon20ins) mutations, highlighting sunvozertinib as an effective treatment for this patient population. The findings have been published in an abstract (#8563) available on the official website of the 2024 American Society of Clinical Oncology's (ASCO) Annual Meeting.

A total of 121 patients with EGFR exon20ins mutations treated with sunvozertinib were included in this biomarker study. Serial plasma ctDNA samples were collected from baseline until disease progression (PD). The key findings of the analysis were as follows:

Antitumor efficacy of sunvozertinib was observed in patients regardless of baseline EGFR exon20ins status in plasma ctDNA.

• There was a positive correlation between detectable EGFR exon20ins in baseline plasma ctDNA and higher number of metastasis sites.
• Higher abundance of EGFR exon20ins in baseline plasma ctDNA was positively correlated with more metastasis sites and brain metastasis (BM).
• Patients with baseline negative EGFR exon20ins in plasma ctDNA achieved a higher objective response rate (ORR) (68.0% vs. 45.8%) and longer median progression free survival (PFS) (7.4 months vs. 5.5 months) than those with positive EGFR exon20ins.

Sunvozertinib could effectively clear EGFR exon20ins in plasma ctDNA, confirming its direct effect on EGFR pathway.

• Decrease of EGFR exon20ins mutant allele was observed in 85.7% of patients with sunvozertinib treatment.
• The earliest clearance of EGFR exon20ins occurred after one week of sunvozertinib treatment.

The resistance to sunvozertinib could be through EGFR-dependent and EGFR-independent mechanisms and combination of golidocitinib, a JAK1 inhibitor, with chemotherapy could be a potential approach to overcome sunvozertinib resistance.

• Acquired EGFR C797S and other genetic aberrations in EGFR downstream signaling pathway may be associated with resistance to sunvozertinib.
• In vitro and in vivo experiments suggested that combination of golidocitinib, a JAK1 inhibitor, with chemotherapy could be a potential approach to overcome sunvozertinib resistance.

"This biomarker study selected for poster presentation at 2024 ASCO Annual Meeting helps us further optimize treatment options for NSCLC patients with EGFR exon20ins mutations, and at the same time validates sunvozertinib's efficiency of clearance of EGFR exon20ins mutations." said Xiaolin Zhang, PhD, CEO of Dizal, "Supported by positive findings from the WU-KONG6 study, a pivotal study with patients from China, sunvozertinib was approved in China in relapsed or refractory setting, making it the world's first and only oral drug for the treatment of NSCLC patients with EGFR exon20ins mutations. The latest data from WU-KONG1 Part B, the equivalent study with patients worldwide, will be unveiled at the upcoming ASCO meeting. The study met its predefined primary end point and was statistically significant, providing substantial evidence for successful NDA submissions of sunvozertinib in the US, the EU and other overseas markets."

WU-KONG1 Part B is a multinational pivotal study, currently being conducted across ten countries and regions in Asia, Europe, North America, and South America. The primary analysis showed that sunvozertinib demonstrated promising antitumor efficacy in relapsed or refractory NSCLC with EGFR exon20ins, with a tolerable safety profile. The updated data will be presented orally at the 2024 ASCO Annual Meeting (Abstract #8513).

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About sunvozertinib (DZD9008)

Sunvozertinib is an irreversible EGFR inhibitor discovered by Dizal scientists targeting a wide spectrum of EGFR mutations with wild-type EGFR selectivity. In August 2023, sunvozertinib received approval from NMPA to treat advanced NSCLC with EGFR exon20ins mutations after platinum-based chemotherapies. The approval is based on the results of WU-KONG6 study, the pivotal study of sunvozertinib in platinum-based chemotherapy pretreated NSCLC with EGFR exon20ins mutations. The primary endpoint of the study was the confirmed overall response rate (cORR) as assessed by the Independent Review Committee (IRC) reached 60.8%. Anti-tumor efficacy was observed across a broad range of EGFR exon20ins subtypes, and in patients with pretreated and stable brain metastasis. In addition, sunvozertinib also demonstrated encouraging anti-tumor activity in NSCLC patients with EGFR sensitizing, T790M, and uncommon mutations (such as G719X, L861Q, etc.), as well as HER2 exon20ins mutations.

Sunvozertinib showed a well-tolerated and manageable safety profile in the clinic. The most common drug-related TEAEs (treatment-emergent adverse event) were Grade 1/2 in nature and clinically manageable.

Two global pivotal studies are ongoing in ≥ 2nd line (WU-KONG1 Part B) and 1st line setting (WU-KONG28), respectively, in NSCLC patients with EGFR exon20ins mutations.

Pre-clinical and clinical results of sunvozertinib were published in peer-reviewed journals Cancer Discovery (IF:39.397) and The Lancet Respiratory Medicine (IF: 76.2).

About Dizal

Dizal is a biopharmaceutical company, dedicated to the discovery, development and commercialization of differentiated therapeutics for the treatment of cancer and immunological diseases. The company aims to develop first-in-class and groundbreaking new medicines, and further address unmet medical needs worldwide. Deep-rooted in translational science and molecular design, it has established an internationally competitive portfolio with two leading assets in global pivotal studies and one already launched. 

To learn more about Dizal, please visit www.dizalpharma.com, or follow us on Linkedin or Twitter.

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