Cullinan Therapeutics said the phase 3 ReziLient3 trial of zipalertinib plus chemotherapy in first-line EGFR exon 20 insertion mutation-positive non-small cell lung cancer cut the median time before disease progression by 6.0 months versus chemotherapy alone.
In the planned interim analysis after 122 progression-free survival events, median progression-free survival was 14.5 months with zipalertinib plus chemotherapy versus 8.5 months with chemotherapy alone. The hazard ratio was 0.50, with a p-value of 0.00015.
Response rates also improved materially: the objective response rate was 65.0% in the combination arm versus 40.3% in the control arm, a gap of 24.7 percentage points. Median duration of response was 14.2 months versus 9.9 months.
Overall survival data were still immature, with 30% event maturity. The hazard ratio for death was 0.72, based on ongoing follow-up.
The trial enrolled 285 adults, including a safety lead-in of six patients. Of the randomized patients, 140 received zipalertinib 100 mg twice daily plus chemotherapy and 139 received chemotherapy alone. Baseline characteristics were closely matched: average age was 66.5 versus 64 years, women made up 65.7% versus 63.3% of each group, and brain metastases were present in 31.4% versus 31.7%.
Safety events were more frequent in the combination arm. Grade 3 or higher adverse events occurred in 87.1% of patients on zipalertinib plus chemotherapy versus 54.4% on chemotherapy alone. The main severe toxicities were hematologic, at 58.6% versus 28.7%. Severe EGFR-related toxicities were uncommon, with rash reported in 10.7% and diarrhea in 1.4% of combination-treated patients. Following these announcements, the company's shares moved -4.15%, and are now trading at a price of $19.735. For the full picture, make sure to review Cullinan Therapeutics's 8-K report.
