Sunvozertinib Receives Breakthrough Therapy Designation for Treatment-Naive EGFR Exon 20+ NSCLC in China

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The Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has granted breakthrough therapy designation (BTD) to sunvozertinib (DZD9008) for the first-line treatment of patients with EGFR exon 20 insertion mutation–positive non–small cell lung cancer (NSCLC) who have not been previously exposed to systemic therapies.¹

This regulatory decision was supported by results from a pooled analysis of the global phase 1/2 WU-KONG1 study (NCT03974022) and the phase 2 WU-KONG15 study (NCT05559645) in China.

According to data presented at the 2023 ESMO Congress, at a median follow-up of 10.8 months, treatment-naive patients (n = 9) achieved a confirmed objective response rate (cORR) of 78.6% and a median progression-free survival (PFS) of 12.4 months with single-agent sunvozertinib when given at the 300 mg dose. The median duration of response was not reached for patients treated with the 300 mg dose. Moreover, 50% of responders treated with the 200 mg or 300 mg dose were still undergoing treatment. All patients achieved tumor shrinkage. The agent was deemed well tolerated and has an overall safety profile comparable to that of classic EGFR-TKIs.^1,2

The agent previously received breakthrough therapy designation (BTD) from the FDA for this same indication in April, 2024. Additionally, both the FDA and CDE granted BTD to sunvozertinib for the treatment of patients with relapsed/refractory EGFR exon 20–mutant NSCLC.¹

Sunvozertinib was approved by the NMPA for use in adult patients with locally advanced or metastatic NSCLC who harbor an EGFR exon 20 insertion mutation and whose disease has progressed on or following platinum-based chemotherapy on August 23, 2023.^1,3

Additional regulatory submissions for market approvals are ongoing.¹

“The total of 4 BTDs by both the US and China’s regulatory agencies, reflects not only sunvozertinib’s transformative potential in EGFR exon 20 insertion [mutation–positive] NSCLC, but also Dizal’s commitment to developing groundbreaking new medicines to address unmet medical needs globally.” Xiaolin Zhang, PhD, chief executive officer of Dizal, stated in a news release.^{1 “}Sunvozertinib is the world first and only oral drug approved for the treatment of lung cancer patients with EGFR [exon 20 insertion mutations]. We are accelerating ongoing clinical studies and regulatory submissions, hoping to bring this new treatment option to more patients as quickly as possible.”

The phase 3, multinational, randomized WU-KONG28 study (NCT05668988) is currently evaluating the efficacy and safety of sunvozertinib compared with platinum doublet chemotherapy in treatment-naive patients with EGFR exon 20–mutant NSCLC who are newly diagnosed or have not received prior systemic therapy for their advanced stage disease.⁴

The study will enroll approximately 320 patients who are at least 18 years of age with cytologically confirmed non-squamous NSCLC. Patients must have stage IIIB/C disease or stage IV disease not suitable for curative therapy, an ECOG performance status of 0 or 1, and at least 1 measurable lesion per RECIST 1.1 criteria. Notably, patients displaying concurrent EGFR mutations, including exon 19 deletions, L858R, T790M, G719X, S768I, or L861Q mutations, are not eligible for the study.

Upon enrollment, patients will be stratified by baseline brain metastasis and randomly assigned 1:1 to receive a daily 300 mg dose of oral sunvozertinib or an initial 6 cycles of platinum-based doublet chemotherapy. Treatment will continue until patients meet discontinuation criterion.

PFS and overall survival serve as the study’s primary and secondary end points, respectively. 

References

1. Sunvozertinib granted breakthrough therapy designation by China CDE for the first-line treatment of non-small cell lung cancer with EGFR exon 20 insertion mutations. News release. Dizal. October 14, 2024. Accessed October 14, 2024. https://www.dizalpharma.com/news/detail?id=79&search=&currentPage=1
2. Yang JCH, Wang M, Chiu CH, et al. Sunvozertinib as first-line treatment in NSCLC patients with EGFR exon20 insertion mutations. Ann Oncol. 2023;34(suppl 2):S765. doi:10.1016/j.annonc.2023.09.2358
3. Dizal’s sunvozertinib approved in China NMPA with potential best-in-class therapy in NSCLC with EGFR exon20ins mutations. News release. Dizal. August 23, 2023. Accessed October 14, 2024. http://www.dizalpharma.com/news/detail?id=59
4. A study of DZD9008 versus platinum-based doublet chemotherapy in local advanced or metastatic non-small cell lung cancer (WU-KONG28). ClinicalTrials.gov. Updated May 23, 2024. Accessed October 14, 2024. https://clinicaltrials.gov/study/NCT05668988