On December 11, 2024 Dizal (SSE:688192), a biopharmaceutical company committed to developing novel medicines for the treatment of cancer and immunological diseases, reported the publication of a pooled analysis evaluating sunvozertinib in epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI)-resistant non-small cell lung cancer (NSCLC) in the official journal of the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Lung Cancer (Press release, Dizal Pharma, DEC 11, 2024, View Source [SID1234649060]). The results of the analysis demonstrated that sunvozertinib exhibited promising antitumor activity and favorable safety profile, warranting future investigations into its potential in patients with EGFR mutated NSCLC who have developed resistance to EGFR TKIs.

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The analysis pooled data from three Phase 1 and 2 studies (WU-KONG1, WU-KONG2 and WU-KONG15). A total of 40 NSCLC patients with EGFR sensitizing mutations who had developed resistance to EGFR TKI treatment were enrolled, 90% of whom had received ≥ 3 prior lines of therapy. Eligible patients received sunvozertinib at doses ranging from 50 mg to 400 mg once daily. As of September 15, 2023, the key findings of the analysis were as follows:

The best objective response rate (ORR) was 27.5 %, and disease control rate (DCR) was 60 %.
The median duration of response (mDoR) and progression free survival (mPFS) were 6.5 months and 6 months, respectively.
Greater ORR of 55.6% was seen in patients with EGFR sensitizing and T790M double mutations (78% had received third-generation EGFR-TKI treatment in prior lines of therapy).
Sunvozertinib was well-tolerated, and the safety profile was consistent with previous reports.
"Resistance to chemotherapy or EGFR TKIs remains a major challenge in the management of EGFR mutated NSCLC. In clinical practice, EGFR-targeted therapeutic strategies are one of the main approaches to addressing EGFR-TKI resistance," said Mengzhao Wang, MD, PhD, at Peking Union Medical College Hospital, the first and corresponding author of the paper. "Sunvozertinib is an oral, irreversible EGFR TKI that targets a broad spectrum of EGFR mutations while maintaining high selectivity for wild-type EGFR. Previous studies suggested that sunvozertinib demonstrated anti-tumor activity in NSCLC patients with EGFR-sensitizing mutations, T790M mutations, and exon 20 insertion mutations. This new analysis further validated sunvozertinib’s potential in overcoming resistance to prior EGFR TKI treatments, warranting further investigation."

"Encouragingly, the pooled analysis has revealed the potential clinical value of sunvozertinib in EGFR TKI-resistant NSCLC," said Xiaolin Zhang, PhD, CEO of Dizal. "Confronted with the challenge of resistance to third-generation EGFR TKIs, we will continue to advance our exploration in this area, aiming to bring new treatment options to patients with EGFR mutated NSCLC."

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 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. 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.

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.

Pre-clinical and clinical results of sunvozertinib were published in peer-reviewed journals Cancer Discovery and The Lancet Respiratory Medicine.