ArriVent firmonertinib misses Phase 3 PFS endpoint in NSCLC

The FURVENT trial's firmonertinib failed to beat chemotherapy on BICR-assessed progression-free survival in first-line EGFR exon 20 insertion-mutant NSCLC.

The Biotech Times Editorial Team By The Biotech Times Editorial Team AI level 2 of 5
AI level 2 of 5: drafted by our AI editorial assistant from the company's announcement; fact-checked, edited and signed off by Mark Walker, Editorial Director. What the levels mean
A brightly lit white medical examination room features a large CT scanner with an illuminated opening and an attached patient table, with wall cabinets and a large window in the background providing natural light.

ArriVent BioPharma has reported that firmonertinib, its oral EGFR inhibitor, did not meet the primary endpoint of progression-free survival (PFS) by blinded independent central review (BICR) in the Phase 3 FURVENT trial. The study evaluated the drug as a first-line treatment for patients with locally advanced or metastatic non-squamous NSCLC harbouring EGFR exon 20 insertion mutations, a subgroup representing roughly 9% of all EGFR-mutant lung cancer cases.

The 398-patient global trial tested firmonertinib at two doses, 240 mg and 160 mg once daily, against platinum-based chemotherapy with pemetrexed. The 240 mg arm produced a median PFS of 11.0 months by BICR versus 9.5 months for the control, with a hazard ratio of 0.75 (95% CI: 0.55, 1.02) and a p-value of 0.0654, falling short of statistical significance. The 160 mg arm returned a median PFS of 8.4 months and a hazard ratio of 0.91, also non-significant.

Where signals emerged

Secondary endpoints offered a more encouraging picture. By investigator assessment, the 240 mg arm achieved a median PFS of 11.1 months versus 7.1 months for chemotherapy, with a hazard ratio of 0.61. Confirmed objective response rates by BICR were 60% and 61% for the 240 mg and 160 mg arms respectively, compared with 33% and 28% for the control. Overall survival data were described as immature but showed a trend toward improvement. The safety profile was broadly manageable: Grade 3 or above treatment-related adverse events were reported in 26% of the 240 mg group and 22% of the 160 mg group, compared with 40% in the chemotherapy arm.

Bing Yao, chairman and chief executive, acknowledged the setback plainly. "These disappointing results are not what we hoped for, particularly for the patients with EGFR exon 20 insertion-mutant NSCLC who urgently need more effective treatment options," he said, adding that the company is evaluating the full dataset to determine the most appropriate development path.

Competitive and regulatory context

The result is a significant setback in a targeted space that has seen intense activity. Amivantamab, a bispecific antibody from Johnson & Johnson's Janssen unit, received FDA approval for EGFR exon 20 insertion-mutant NSCLC in 2021, and mobocertinib had a prior accelerated approval before its voluntary withdrawal in 2023. Amivantamab plus lazertinib and amivantamab plus chemotherapy have since generated data in the broader EGFR-mutant population, raising the competitive bar. The divergence between BICR and investigator-assessed PFS in FURVENT, a gap of 11.0 versus 11.1 months for the 240 mg arm but 9.5 versus 7.1 months for chemotherapy by the two review methods, may prompt detailed scrutiny of trial conduct when full data are presented at a forthcoming conference.

Firmonertinib retains its FDA Breakthrough Therapy Designation for this indication and is approved in China for EGFR classical mutations and for exon 20 insertions in previously treated patients. ArriVent is also running ALPACCA, a separate Phase 3 study in first-line NSCLC patients with EGFR PACC mutations, which remains ongoing. The company's next steps in the exon 20 insertion setting, whether a refined patient selection strategy, a combination approach, or a regulatory discussion about the secondary endpoint data, will be closely watched by investors and the broader oncology community.

Sector

Topic

Geography