New drug for Exon 20+ NSCLC likely…'zipalertinib' results

A TKI jointly developed by Taiho Pharmaceutical and Cullinan Therapeutics, 33% overall response rate (ORR) in Asian cohort

Secured administration convenience and safety profile…becoming a competing drug against Rybrevant

The oral EGFR Exon 20 insertion mutation targeted therapy, zipalertinib, jointly developed by Japan's Taiho Pharmaceutical and the U.S.'s Cullinan Therapeutics, demonstrated consistent efficacy in the Asian patient cohort. Zipalertinib has become as a potential competing drug against Janssen’s 'Rybrevant (amivantamab)', which is currently the only approved first-line therapy in this area.

According to industry sources on December 8, clinical results for zipalertinib were presented at the recent European Society for Medical Oncology Asia (ESMO Asia 2025) annual meeting in Singapore. This analysis was a subgroup analysis of the Asian population, following the initial data presented at the American Society of Clinical Oncology (ASCO) 2025, and evaluated zipalertinib's clinical utility in Exon 20 insertion-mutated Non-Small Cell Lung Cancer (NSCLC).

Despite EGFR Exon 20 insertion-mutated NSCLC being a relatively higher prevalence in Asia, there have been limited treatment options for this disease. Following Takeda's market withdrawal of 'Exkivity (mobocertinib)', only Rybrevant remains, leaving a significant unmet need for new agents. Analysis suggests that the Asian subgroup analysis results for the orally administered zipalertinib are likely attracting considerable industry attention.

Professor Ross A. Soo of the National University Cancer Institute Singapore

The study enrolled 137 patients, of whom 107 were Asian, and 30 were from the Rest of the World (ROW). Efficacy analysis was conducted in 176 patients with at least 8 months of follow-up. Patients were administered zipalertinib 100 mg twice daily, and approximately half of the cohort (41%) had a history of brain metastases.

The overall response rate (ORR) showed minimal difference between the two groups: 33% for the Asian cohort and 37% for the ROW cohort. The duration of response (DOR) was 8.3 months for the Asian cohort and 10.5 months for the ROW cohort. The progression-free survival (PFS) was 9.5 months in the Asian cohort and 9.0 months in the ROW cohort, with almost identical efficacy curves.

The median overall survival (OS) has not yet been reached in the Asian cohort, compared with 24 months in the ROW cohort. The investigators assessed that "zipalertinib demonstrated a clinically meaningful and consistent response in both Asian and non-Asian populations."

The safety profile also showed no significant differences between the two groups. The most common adverse events (AEs) were paronychia, rash, dry skin, stomatitis, and diarrhea, which are generally manageable AEs associated with the Tyrosine Kinase Inhibitor (TKI) class. Even considering that Asian patients tend to show a higher incidence of certain AEs like skin and hand-foot syndrome with targeted therapies, zipalertinib demonstrated a manageable tolerability.

Professor Ross A. Soo of the National University Cancer Institute Singapore explained, "Zipalertinib demonstrated efficacy in Asian patients comparable to the global patient population, confirming its potential as a new treatment option," and added, "The fact that it is an oral agent also holds significant value in terms of treatment adherence and accessibility."

Based on these clinical results, Taiho Pharmaceutical and Cullinan Therapeutics have initiated the New Drug Application (NDA) submission process in the United States.