Dizal Unveils Encouraging Results for Sunvozertinib in EGFR TKI-Resistant NSCLC

Dizal, a pioneering biopharmaceutical enterprise focused on creating groundbreaking treatments for cancer and immune system ailments, has announced the release of a comprehensive analysis assessing sunvozertinib’s efficacy in non-small cell lung cancer (NSCLC) patients resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). This significant analysis was published in ESMO Lung Cancer, the authoritative publication of the European Society for Medical Oncology.

The review of the data showed that sunvozertinib possesses notable tumor-fighting properties alongside a favorable safety profile, highlighting the need for further exploration of its application in patients with mutations in EGFR who have developed resistance to EGFR TKIs.

The assessment consolidated findings from three phase 1 and 2 trials, namely WU-KONG1, WU-KONG2, and WU-KONG15. These trials included 40 patients with NSCLC and specific EGFR mutations who had developed resistance after EGFR TKI treatments, with 90% having undergone at least three prior therapies. Doses ranging from 50 mg to 400 mg were administered to eligible participants once daily. As per data collected up to September 15, 2023, the analytical findings highlighted:

  • A 27.5% optimal objective response rate (ORR) and a 60% disease control rate (DCR).
  • Median durations for response (mDoR) and progression-free survival (mPFS) set at 6.5 months and 6 months, respectively.
  • An increased ORR of 55.6% noted in patients with EGFR sensitizing and T790M mutations, of which 78% had received third-generation EGFR-TKI treatments prior.

Sunvozertinib demonstrated good tolerability, aligning well with previous safety data.

“Ongoing challenges in managing NSCLC with EGFR mutations include the development of resistance to chemotherapeutic or EGFR TKIs,” highlighted Mengzhao Wang from Peking Union Medical College Hospital and the lead author of the paper. “The targeted therapeutic approach for EGFR-TKI resistance leverages EGFR-specific strategies. Sunvozertinib, an oral irreversible EGFR TKI, encompasses comprehensive targeting of EGFR mutations while maintaining selectivity for the wild-type variant. Previous assessments have shown its efficacy in patients exhibiting EGFR-sensitizing, T790M, and exon 20 insertion mutations. This pooled analysis corroborates sunvozertinib’s potential to counteract treatment resistance, meriting further investigation.”

Xiaolin Zhang, PhD and CEO of Dizal, remarked, “Promising findings from the pooled analysis highlight sunvozertinib’s clinical promise in battling EGFR TKI-resistant NSCLC. As we tackle resistance issues regarding third-generation EGFR TKIs, we are committed to further enhancing our research, aspiring to introduce new treatment avenues for patients with mutated EGFR NSCLC.”

Sunvozertinib, a groundbreaking irreversible EGFR inhibitor conceptualized by Dizal experts, targets a broad spectrum of EGFR mutations with selectivity for the wild-type variant. In August 2023, the NMPA approved sunvozertinib for advanced NSCLC with EGFR exon20ins after prior platinum-based chemotherapy treatments. This approval stemmed from the WU-KONG6 study, demonstrating a confirmed overall response rate (cORR) of 60.8%, as evaluated by an Independent Review Committee. The trial confirmed sunvozertinib’s anti-tumor properties across diverse EGFR exon20ins subtypes, including patients with pre-treated brain metastasis. Additionally, sunvozertinib showed efficacy in NSCLC individuals with EGFR sensitizing, T790M, and uncommon mutations (such as G719X, L861Q), and HER2 exon20ins.

The safety profile of sunvozertinib was well-tolerated, with mostly Grade 1/2 TEAEs (treatment-emergent adverse events) considered manageable clinically.

Ongoing are two pivotal global trials addressing = 2nd line (WU-KONG1 Part B) and 1st line (WU-KONG28) scenarios for NSCLC patients with EGFR exon20ins.