NSCLC is increasingly becoming a biomarker-driven market. EGFR is one of the profitable biomarker segments, with blockbuster therapies such as TAGRISSO. TAGRISSO is now the dominant EGFR inhibitor. The prevalence of patients with this resistance mutation has increased since TAGRISSO was authorized for use in the first line. The post-TAGRISSO setting is one of the highest areas of unmet need.  

Sunvozertinib is an irreversible EGFR inhibitor discovered by Dizal Pharmaceuticals’ scientists targeting a wide spectrum of EGFR mutations with wild-type EGFR selectivity. Primary analysis data of sunvozertinib was presented at the ASCO conference, highlighting the topline results from its WU-KONG1 Part B study (NCT03974022; ≥ 2nd line). It is a multinational pivotal study, currently being conducted across ten countries and regions in Asia, Europe, North America, and South America. WU-KONG1 has a similar study design as WU-KONG6. 

During the conference, it was revealed that the WU-KONG1B study achieved its primary objective, with a manageable safety profile in platinum-based chemotherapy pretreated NSCLC with EGFR exon20ins. As of March 22, 2024, 111 patients had been recruited to receive the best recommended phase 2 dosage (RP2D) of sunvozertinib, which is 300 mg. Data revealed that sunvozertinib had the highest ORR of 53.3% according to the IRC assessment. The DoR rate at nine months was 57%. In patients who had previously had amivantamab therapy or not, the best ORRs were 50% and 53.8%, respectively. Similar AE profile to previously reported. 

KOL insights

“This biomarker study selected for presentation at 2024 ASCO Annual Meeting helps to further optimize treatment options for NSCLC patients with EGFR exon20ins mutations, and at the same time validates sunvozertinib's efficiency of clearance of EGFR exon20ins mutations” – Expert Opinion. 

Conclusion:

In the United States, two therapies, RYBREVANT (Johnson & Johnson) and EXKIVITY (Takeda), were approved for the niche EXON-20 mutant NSCLC segment. EXON-20 mutant NSCLC is currently an unproven market with a small addressable market (10–12% of EGFR NSCLC). Companies like Cullinan oncology/Taiho Oncology, ArriVent BioPharma, and Dizal Pharmaceutical, are aiming at the EXON-20 mutant EGFR NSCLC segment. In October 2023, Takeda announced plans to voluntarily withdraw EXKIVITY in the United States for adult patients with EGFR exon 20. Therefore at present, RYBREVANT is the key therapy in this segment. Johnson & Johnson with RYBREVANT is aiming to access a broader EGFR pool to maximize its market opportunity.

Sunvozertinib represents a groundbreaking achievement as the first Chinese innovative drug approved for EGFR exon 20 insertion NSCLC. In August 2023, sunvozertinib received approval from NMPA making it the first oral drug ever developed to treat advanced NSCLC with EGFR exon20ins mutations after platinum-based chemotherapies. The approval was based on the results of the WU-KONG6 study, the pivotal study of sunvozertinib in platinum-based chemotherapy pretreated NSCLC with EGFR exon20ins mutations. The primary endpoint of the study was the confirmed ORR as assessed by the Independent Review Committee (IRC) reached 60.8%. Sunvozertinib has also been granted Breakthrough Therapy Designation by both the US FDA and China NMPA in treating NSCLC with EGFR exon20ins.  Sunvozertinib was previously granted  BTDs by both the US FDA and the China Center for Drug Evaluation (CDE) for relapsed or refractory patients  It was subsequently approved in China in 2023 for the treatment of patients who failed 1st line treatment. The company is expecting NDA submission for the US and EU approvals for the treatment of patients who failed 1st line treatment  in 2024.

The achievement of its primary objective in the WU-KONG1B study, coupled with its Breakthrough Therapy Designation and approval in China, underscores its significance in lung cancer treatment. At present, the company is advancing the development of sunvozertinib in the first-line setting of NSCLC with EGFR exon20ins through a global phase III study (WU-KONG28). In conclusion, Sunvozertinib emerges as a promising aspect for NSCLC patients with EGFR exon20ins mutations, supported by its potent EGFR inhibition and demonstrated efficacy across global clinical trials.