Dizal Highlights Sunvozertinib's Effectiveness for EGFR Exon 20 Non-small Cell Lung Cancer

Dizal, a biopharmaceutical company, recently disclosed promising results from a biomarker study focused on non-small cell lung cancer (NSCLC) patients carrying EGFR exon 20 insertion (exon20ins) mutations. The study, which was discussed at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, evaluated the therapeutic efficacy of sunvozertinib, marking a significant step forward in the treatment of this specific cancer subtype.

Study Overview

The biomarker study included 121 patients with EGFR exon20ins mutations who were administered sunvozertinib. Plasma ctDNA samples were collected from these patients at baseline and monitored until disease progression. Key findings from the study indicated sunvozertinib's potent antitumor activity irrespective of the baseline EGFR exon20ins status in plasma ctDNA. Notably, the presence of EGFR exon20ins in baseline plasma ctDNA correlated with a higher number of metastasis sites, including brain metastasis.

Key Findings

1. Antitumor Efficacy: Sunvozertinib demonstrated significant antitumor efficacy in patients, regardless of whether EGFR exon20ins was detectable in their baseline plasma ctDNA.

2. Correlation with Metastasis: A higher abundance of EGFR exon20ins in baseline plasma ctDNA was positively correlated with more metastasis sites and brain metastasis.

3. Response Rate and Survival: Patients with undetectable EGFR exon20ins in their baseline plasma ctDNA achieved a higher objective response rate (68.0% vs. 45.8%) and a longer median progression-free survival (7.4 months vs. 5.5 months) compared to those with detectable mutations.

4. Clearance of Mutations: Sunvozertinib proved effective in clearing EGFR exon20ins in plasma ctDNA, with a decrease in mutant alleles observed in 85.7% of patients. The earliest mutation clearance was seen as soon as one week after initiating treatment.

Overcoming Resistance

The study also explored the resistance mechanisms to sunvozertinib, which can be both EGFR-dependent and EGFR-independent. A combination therapy involving golidocitinib, a JAK1 inhibitor, and chemotherapy was proposed as a potential strategy to overcome this resistance. Acquired EGFR C797S and other genetic aberrations in downstream signaling pathways were identified as contributors to resistance. Both in vitro and in vivo experiments suggested the efficacy of this combination therapy.

Implications and Future Directions

Xiaolin Zhang, CEO of Dizal, emphasized the significance of these findings for optimizing treatment for NSCLC patients with EGFR exon20ins mutations. The results from the WU-KONG6 study in China, which led to the approval of sunvozertinib for relapsed or refractory NSCLC, were particularly encouraging. Sunvozertinib is currently the only oral drug approved for this indication globally.

The multinational WU-KONG1 Part B study, which includes patients from across Asia, Europe, North America, and South America, also demonstrated promising antitumor efficacy and a tolerable safety profile. The updated results will be presented at the upcoming ASCO meeting, providing substantial evidence for regulatory submissions in the US, EU, and other markets.

About Sunvozertinib

Sunvozertinib is an irreversible EGFR inhibitor targeting a broad spectrum of EGFR mutations while sparing wild-type EGFR. It has shown efficacy in NSCLC patients with a variety of EGFR mutations, including exon20ins, sensitizing, T790M, and uncommon mutations, as well as HER2 exon20ins mutations. The drug has a well-tolerated safety profile, with most treatment-emergent adverse events being manageable.

Two global pivotal studies are currently underway to further evaluate sunvozertinib in NSCLC patients with EGFR exon20ins mutations.

Conclusion

Dizal’s study reaffirms sunvozertinib's potential as an effective treatment for NSCLC patients with EGFR exon20ins mutations, offering hope for better management of this challenging cancer subtype. With ongoing research and upcoming presentations, the medical community eagerly anticipates further advancements in this field.

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