firmonertinib misses primary endpoint in phase 3 lung cancer trial, setting back evidence of first-line efficacy

For patients with advanced lung cancer harboring specific EGFR mutations, whether an oral targeted drug can control disease longer than chemotherapy is an important test for its use as a first-line treatment. ArriVent BioPharma announced on October 6 that firmonertinib did not meet the primary efficacy endpoint in the pivotal phase 3 FURVENT trial, prompting a reassessment of the development program.

FURVENT enrolled 398 patients with locally advanced or metastatic nonsquamous non-small cell lung cancer harboring EGFR exon 20 insertion mutations who had not previously received systemic anticancer therapy. The trial compared once-daily firmonertinib at 160 mg and 240 mg with a chemotherapy regimen combining a platinum agent and pemetrexed. The central question was whether it could extend the time before disease progression or death, known as progression-free survival (PFS).

According to blinded independent central review, median PFS was 11.0 months in the 240 mg group and 9.5 months in the chemotherapy group, with a p-value of 0.0654, which did not reach statistical significance. The hazard ratio was 0.75, with a 95% confidence interval of 0.55 to 1.02, encompassing 1, the value indicating no difference. This means the data favored firmonertinib but were insufficient to establish superiority on the primary endpoint.

Other efficacy measures provided different clues. The independently confirmed objective response rate—the proportion of patients whose tumor shrinkage met predefined criteria—was 60% in the 240 mg group and 33% in the chemotherapy group. However, tumor shrinkage in more patients does not guarantee longer disease control; this is also why response rate cannot replace the primary endpoint.

Results also differed between assessment methods: investigator-assessed median PFS was 11.1 months in the 240 mg group and 7.1 months in the chemotherapy group, a larger gap than in the independent review. This secondary analysis can provide supplementary information, but the trial's success must still be judged against the prespecified primary endpoint, rather than by substituting a more favorable assessment result.

The company said the safety profile was consistent with previous studies and that no new safety signals were identified; this does not mean the treatment has no side effects. Overall survival data remain immature, and the trend toward improvement described in the announcement cannot currently be interpreted as proven prolongation of life.

ArriVent will review the full data before deciding on the future development direction for firmonertinib. What can currently be confirmed is that this trial did not establish its superiority on the primary efficacy endpoint as a first-line treatment in the target population. Publicly available information still consists mainly of the company's summary. More complete analyses are needed to understand why the assessments differed, which patients might benefit, and how survival outcomes evolve.