Cullinan and Taiho Unveil Promising Lung Cancer Data, Plan FDA Application

Cullinan Therapeutics and Taiho Oncology have released encouraging data from their pivotal phase 2b trial of zipalertinib, a novel EGFR tyrosine kinase inhibitor, in patients with pretreated EGFR ex20ins non-small cell lung cancer (NSCLC). The results, which will be presented at the upcoming American Society of Clinical Oncology (ASCO) annual meeting, have prompted the companies to pursue an accelerated approval application with the FDA.

Impressive Efficacy Results

The phase 2b cohort of the Rezilient1 study demonstrated an overall objective response rate (ORR) of 35% in patients treated with twice-daily oral doses of zipalertinib. The median duration of response (mDOR) was 8.8 months at 24 months, meeting both of the study's primary endpoints.

In patients who had previously received only platinum-based chemotherapy, the ORR increased to 40% with a consistent mDOR of 8.8 months. For those with brain metastases, the ORR was 31% with an mDOR of 8.3 months.

Safety Profile and Patient Population

The safety analysis included 244 patients who received at least one dose of 100 mg zipalertinib. The most common treatment-related adverse events were paronychia (nail infections) in 38.5% of patients and rash in 30.3%. While most adverse events were grade 1 or 2, anemia was the most frequent severe event, occurring in 7% of patients.

The efficacy population comprised 176 patients who had received a median of two prior therapies, with 39% having a history of brain metastases.

Regulatory and Development Plans

Zipalertinib has already received breakthrough therapy designation from the FDA. Cullinan and Taiho plan to submit an approval application for relapsed or refractory EGFR ex20ins NSCLC in the second half of 2025.

Dr. Helena Yu, a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center, highlighted the urgent need for well-tolerated targeted therapies in this patient population, stating, "The findings from the REZILIENT1 trial may support zipalertinib as a potential new oral treatment option for patients whose disease progressed after prior therapies."