Pooled Data Show Sunvozertinib Potential in EGFR-Mutated NSCLC

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Data from a pooled analysis evaluating sunvozertinib (formerly DZD9008) show promising antitumor activity with a favorable safety profile for EGFR- tyrosine kinase inhibitor (TKI)-resistant non–small cell lung cancer (NSCLC). The pooled data come from 3 studies: the multinational phase 2 WU-KONG1 trial (NCT03974022), the phase 1 WU-KONG2 trial (CTR 20192097) and the phase 2 WU-KONG15 trial (NCT05559645).¹

“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.”

The pooled analysis included a combined total of 40 patients with EGFR mutated NSCLC who had developed resistance to TKI treatment. Of these, 90% had received 3 or more prior lines of therapy with a median of 5 lines (range 1-16).^1,2 All patients had received prior treatment with at least 1 type of EGFR TKI and 68.8% of patients received third generation EGFR TKI. Most patients also received prior chemotherapy (90.6%).

In these studies, doses of sunvozertinib ranged from 50 mg to 400 mg received daily. Antitumor activity was seen starting from a dose of 50 mg regardless of T790M mutation status.²

As of September 15, 2023, the agent elicited a 27.5% objective response rate (ORR) and a 60% disease control rate. The median duration of response was 6.5 months, and median progression-free survival lasted for 6 months. Patients with both EGFR sensitizing and T790M mutations had a higher ORR of 55.6%, with most having previously been treated with third-generation EGFR TKIs.

At baseline, the median age was 64.5 years, 68.8% of patients were female, and 75% had an ECOG performance status of 1. In addition, 34.4% had more than 3 metastatic sites, and 43.8% had brain metastases at baseline.²

Regarding safety, sunvozertinib’s profile was manageable and well-tolerated across all dose levels, consistent with previous findings, according to investigators.

To be eligible for the phase 2 WU-KONG15 trial patients must be 18 years or older with histologically or cytologically confirmed locally advanced or metastatic NSCLC and documented EGFR mutations.³ They should have an ECOG performance status of 0 or 1, a predicted life expectancy of at least 12 weeks, and measurable disease as per RECIST 1.1 criteria. Patients must have either progressed or been intolerant to standard therapy, except those in specific cohorts, specifically, cohort 4 with EGFR exon 20 insertions(exon20ins), cohort 5 with EGFR sensitizing mutations, and cohort 7 for those treatment-naive. Those with brain metastases may be included if stable, neurologically asymptomatic, and not requiring corticosteroids. Adequate organ function is also required for participation, investigators noted. The eligibility criteria for the phase 2 WU-KONG1 trial had some minor differences, including more specific inclusion requirements for both EGFR and HER2 mutations, prior treatment of brain metastases, and guidelines for prior therapies.⁴

Currently, there are 2 ongoing global studies that further evaluate sunvozertinib in NSCLC with EGFR exon20ins: WU-KONG1 part B in the second-line setting and beyond, and the phase 3 multinational, randomized WU-KONG28 study (NCT05668988) in the first-line setting.

“Resistance to chemotherapy or EGFR TKIs remains a major challenge in the management of EGFR-mutated NSCLC.” said Mengzhao Wang, MD, PhD, lead author, Peking Union Medical College Hospital, China. “Sunvozertinib is an oral, irreversible EGFR TKI that targets a broad spectrum of EGFR mutations in addition to maintaining high selectivity for wild-type EGFR. Previous studies suggested that sunvozertinib demonstrated antitumor activity in patients with NSCLC with EGFR-sensitizing mutations, T790M mutations, and exon 20 insertion mutations.⁵This new analysis further validated sunvozertinib’s potential in overcoming resistance to prior EGFR TKI treatments, warranting further investigation.”

In China, sunvozertinib received approval from the National Medical Products Administration in August 2023 for the treatment of advanced NSCLC with EGFR exon20ins after platinum-based chemotherapies. Data from the WU-KONG6 study supported the approval in China.⁶

References

1. Dizal announces positive pooled data of sunvozertinib in EGFR tyrosine kinase inhibitor-resistant non-small cell lung cancer published in lung cancer. News release. December 11, 2024. Accessed January 23, 2025. https://tinyurl.com/ybhynbyd

2. Yang JCH, Xu Y, Huang WT, et al. Anti-tumor activity of sunvozertinib in NSCLC with EGFR sensitizing mutations after failure of EGFR TKI treatment. J Clin Oncol 2023;41(16_suppl):9103-9103. doi 10.1200/jco.2023.41.16_suppl.9103

3. Assessing an oral EGFR inhibitor, sunvozertinib in patients who have advanced non-small cell lung cancer with EGFR or HER2 mutation (WU-KONG1). Clinicaltrials.gov. Updated December 12, 2025. Accessed January 23, 2025. https://www.clinicaltrials.gov/study/NCT03974022

4. Assessing an oral EGFR inhibitor, DZD9008 in patients with advanced non-small cell lung cancer (NSCLC) with EGFR mutations (WU-KONG15) (WU-KONG15). Clinicaltrials.gov. Last updated May 29, 2024. Accessed January 23, 2025. https://www.clinicaltrials.gov/study/NCT05559645

5. Wang M, Yang JCH, Mitchell PL, et al. Sunvozertinib, a selective EGFR inhibitor for previously treated non-small cell lung cancer with EGFR exon 20 insertion mutations. Cancer Discov. 2022;12(7):1676-1689. doi.10.1158/2159-8290.CD-21-1615

6. Sunvozertinib tablets approved for marketing by China NMPA. Nmpa.gov.cn. August 23, 2023. Accessed January 23, 2025. https://english.nmpa.gov.cn/2023-08/23/c_964025.htm