CAMBRIDGE, Mass. — Taiho Oncology and Cullinan Therapeutics announced positive results from a Phase 2 clinical trial evaluating zipalertinib in patients with advanced non-small cell lung cancer (NSCLC) carrying EGFR exon 20 insertion or other uncommon EGFR mutations and active brain metastases.
The findings from Cohort C of the REZILIENT2 trial demonstrated clinically meaningful antitumor activity in the brain, with an intracranial objective response rate of 30.2% among 43 evaluable patients.
The results will be presented at the European Society for Medical Oncology (ESMO) Congress 2026, scheduled for October 23-27 in Madrid, Spain.
Among the 43 patients evaluated, zipalertinib achieved an intracranial disease control rate of 72.1% and a median intracranial duration of response of 9.7 months. Patients who had not previously received EGFR tyrosine kinase inhibitor therapy experienced a higher intracranial response rate of 37.5%.
“Patients with NSCLC harboring EGFR exon 20 insertion mutations or other uncommon EGFR mutations and active CNS metastases have a significant need for therapies that can effectively address disease in the brain,” said Helena A. Yu, MD, thoracic medical oncologist at Memorial Sloan Kettering Cancer Center and a study investigator.
“The intracranial responses observed with zipalertinib in REZILIENT2 are encouraging and support continued evaluation of zipalertinib in this difficult-to-treat patient population,” Yu added.
The study enrolled 59 patients with locally advanced or metastatic NSCLC and active central nervous system metastases, including patients with leptomeningeal disease, a condition in which cancer spreads to the membranes surrounding the brain and spinal cord.
At the data cutoff, the median follow-up was 9.2 months. Among the 43 evaluable patients, 67.4% had EGFR exon 20 insertion mutations, and 44.2% had previously received EGFR tyrosine kinase inhibitors. Patients had received a median of two prior lines of treatment.
Zipalertinib, administered at 100 mg twice daily, was generally well tolerated. The most common treatment-related adverse events included inflammation around the fingernails or toenails, reported in 32.6% of patients, and diarrhea, reported in 25.6%. Severe treatment-related adverse events occurred in 20.9% of patients.
“The REZILIENT2 results reflect a rigorous examination of the CNS activity of zipalertinib as monotherapy in patients with EGFR ex20ins or uncommon EGFR-mutated NSCLC and active CNS metastases,” said Harold Keer, MD, PhD, chief medical officer of Taiho Oncology.
“The findings add to the growing clinical evidence supporting the continued evaluation of zipalertinib in patients with EGFR-mutated NSCLC and brain involvement,” Keer added.
Jeffrey Jones, MD, MBA, chief medical officer of Cullinan Therapeutics, said the findings reinforce the potential of zipalertinib in patients with limited treatment options.
“The REZILIENT program was designed to explore zipalertinib’s potential in clinically important settings where additional treatment options are needed,” Jones said. “Today’s REZILIENT2 update extends that commitment by providing evidence of intracranial activity in patients with active CNS metastases.”
