#USA #Princeton #Taiho Oncology #Cullinan Therapeutics #Zipalertinib

Introduction

At the recent ESMO Congress 2025, held in late October, Taiho Oncology, Inc. and Cullinan Therapeutics, Inc. presented significant findings from the ongoing REZILIENT2 study demonstrating the efficacy of zipalertinib in treating patients with advanced non-small cell lung cancer (NSCLC) who have specific genetic mutations and active brain metastases. This mini oral presentation has captured the attention of oncologists and researchers aiming to improve treatment modalities for this traditionally difficult-to-treat patient population.

Study Overview

Zipalertinib is an innovative oral tyrosine kinase inhibitor specifically designed to target emerging activations in the epidermal growth factor receptor (EGFR). Focused on patients with EGFR exon 20 insertion mutations, the latest data quantifies results from the central nervous system (CNS) involvement cohort of the Phase 2b REZILIENT2 trial. Dr. Helena A. Yu from Memorial Sloan Kettering Cancer Center emphasized the dire need for effective treatment due to the high incidence of brain metastases in NSCLC patients with EGFR exon 20 insertions, which ranges from 23% to 39%. These patients often face poor prognoses and require aggressive therapy including surgery and radiotherapy.

Preliminary Efficacy Results

As of the data cutoff in February 2025, the CNS involvement cohort of 32 patients reported encouraging outcomes when administered zipalertinib at a dose of 100 mg twice daily. Of note, preliminary data demonstrated:

• - Intracranial Objective Response Rate (iORR): 31.3%, which includes one complete response.
• - Intracranial Disease Control Rate (iDCR): 68.8% demonstrating the drug's capacity to halt disease progression within the CNS.
• - Median Intracranial Duration of Response (DOR): 8.1 months, highlighting prolonged responses in patients.
• - Preliminary systemic ORR was documented at 27.6% with a median DOR of 7.6 months.

These findings suggest that zipalertinib not only offers a potential avenue for treatment but performs comparably to systemic treatment responses seen in wider NSCLC patient populations. The research advocates for the continuation of investigations into zipalertinib's broader applications.

Safety and Tolerability Insights

Regarding safety, zipalertinib was well-tolerated among most patients. Notably, no new safety signals emerged during the trial. However, treatment-related adverse events of Grade 3 or higher were reported, affecting 25% of the patients and included anemia and interstitial lung disease. Unfortunately, one death was attributed to interstitial lung disease, underscoring the necessity for continuous monitoring and support for patients undergoing zipalertinib treatment.

Future Directions

The REZILIENT2 study places a significant emphasis on addressing the unmet medical needs of NSCLC patients with GF mutations and brain metastases. The study is pivotal not only in delivering new data but in shaping the directive for future clinical explorations. Patients enrolled in Cohort C, focusing on active brain metastases, may pave the way for future therapeutic strategies.

Conclusion

In summary, Taiho Oncology and Cullinan Therapeutics's presentation at ESMO Congress 2025 sheds light on the promising potential of zipalertinib in a cohort previously underserved in treatment options. As research continues, the medical community hopes to further refine the therapeutic landscape for patients grappling with the challenges posed by NSCLC and its associated complications, particularly CNS metastases. The encouraging results serve as a beacon for optimism, affirming the commitment from both companies to push forward in the battle against cancer.