Sunvozertinib Approved in China for NSCLC With EGFR Exon 20 Insertion Mutations

The National Medical Products Administration of China has approved sunvozertinib (DZD9008) for use in adult patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations whose disease has progressed on or following platinum-based chemotherapy.¹

The regulatory decision is supported by finding yielded in the phase 2 WO-KONH6 trial (NCT05712902). When sunvozertinib was given at the recommended phase 2 dose of 300 mg daily, it elicited an objective response rate (ORR) of 60.8% (95% CI, 50.4%-70.6%; P < .0001); this was comprised entirely of partial responses.² The stable disease rate was 26.8% and the progressive disease rate was 6.2%; 6.2% of patients were not evaluable for response. Moreover, the disease control rate (DCR) with the agent was 87.6% (95% CI, 79.4%-93.4%).

“In pretreated advanced NSCLC patients with EGFR exon 20 insertion mutations, monotherapy with sunvozertinib achieved a remarkable ORR of 60.8%,” Professor Mengzhao Wang, MD, PhD, lead principal trial investigator, of the Peking Union Medical College Hospital, stated in a press release.¹ “This treatment demonstrated comparable efficacy to traditional EGFR TKIs in treating pretreated advanced NSCLC patients with EGFR sensitizing mutations. The approval of sunvozertinib is expected to change the current treatment dilemma for patients with EGFR exon 20 insertion–mutant advanced NSCLC, providing them with more effective and safer treatment options.”

The WU-KONG6 study enrolled patients with locally advanced or metastatic NSCLC whose tumors harbored EGFR exon 20 insertion mutations.² These patients had previously received 1 to 3 lines of systemic therapies and experienced disease progression on or following platinum-based chemotherapy.

Study participants were administered sunvozertinib at a daily dose of 300 mg. ORR by independent review committee (IRC) assessment served as the primary end point. Key secondary end points included IRC-assessed duration of response (DOR); investigator-assessed ORR, progression-free survival, DCR, and changes in tumor size; overall survival; safety and tolerability; and pharmacokinetics.

At the time of the data cutoff date of October 17, 2022, 104 patients had been enrolled to the trial, and 97 were included in the efficacy analysis set. The median age was 58 years (range, 29-79), and 59.8% were female. Moreover, 67% of patients did not have a history of smoking, and 32% had brain metastasis at baseline. Regarding mutation subtypes, 39.2% had 769_ASV mutations, 17.5% had 770_SVD mutations, and 43.3% had others.

The median number of prior therapies received was 2, with a range of 1 to 3. All patients received prior platinum-based chemotherapy. Other prior treatments included EGFR TKIs (26.8%), PD-1 or PD-L1 inhibitors (35.1%), anti-VEGF inhibitors (59.8%), and others (16.5%).

Additional data presented at the 2023 ASCO Annual Meeting showed that over 90% of patients experienced tumor shrinkage with sunvozertinib. Notably, responses were achieved in those who previously received amivantamab and in those with baseline brain metastases.

Data from a subgroup analysis indicated that sunvozertinib had efficacy regardless of age (<65 years, ORR, 56.5%; ≥65 years, 71.4%), sex (female, 60.3%; male, 61.5%), smoking status (never, 66.2%; smokers, 50%), brain metastases at baseline (yes, 48.4%; no, 66.7%), prior lines of therapy (<3 regimens, 61.7%; 3, 56.3%), mutation subtypes (769_ASV, 63.2%; 770_SVD, 58.8%; other, 59.5%), and previous exposure to PD-1 or PD-L1 agents (yes, 55.9%; no, 63.5%).

The median duration of treatment for patients was 7.0 months, with the longest duration of therapy being 19.2 months. At a median follow-up of 5.6 months following response, 64.4% of the 59 responders were still responding to treatment. The median DOR had not yet been reached, and the longest DOR was longer than 11.2 months.

Regarding safety, common treatment-emergent toxicities reported with sunvozertinib in the 104 total patients included diarrhea (any grade, 67.3%; grade ≥3, 7.7%), increased blood CPK (57.7%; 17.3%), rash (53.8%; 1%), anemia (49%; 5.8%), increased blood creatinine (37.5%; 0%), paronychia (32.7%; 1.9%), decreased weight (28.8%; 1.0%), decreased white blood cells (26%; 0%), increased lipase (26%; 1.9%), vomiting (24%; 1%), decreased appetite (24%; 1.9%), and mouth ulceration (23.1%; 0%).

“Sunvozertinib represents a groundbreaking achievement as the first Chinese innovative drug approved for EGFR exon 20 insertion NSCLC, showcasing Dizal’s remarkable efficiency and unwavering commitment to innovation,” Xiaolin Zhang, PhD, chairman and chief executive officer of Dizal, stated in a press release.¹ “Our achievement of obtaining new drug application approval in less than 4 years from enrolling the first patient sets an unprecedented benchmark for the rapid development of targeted lung cancer treatments. We are thrilled to bring sunvozertinib, the potentially best-in-class targeted therapy, to patients in China.”

References

1. 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 August 23, 2023. http://www.dizalpharma.com/news/detail?id=59
2. Wang M, Fan Y, Sun M, et al. Sunvozertinib for the treatment of NSCLC with EGFR exon20 insertion mutations: the first pivotal study results. J Clin Oncol. 2023;41(suppl 16):9002. doi:10.1200/JCO.2023.41.16_suppl.9002