ArriVent Misses Phase 3 PFS Goal For Firmonertinib In 398-Patient NSCLC Trial, Sending Shares Down 57%

ArriVent BioPharma said its phase 3 Furvent trial of firmonertinib missed the primary endpoint of progression-free survival by blinded independent central review, a result that pushed the company's stock down 57% in early trading. The miss is a material setback because Furvent was intended to support a chemotherapy-free first-line option in a setting where Johnson & Johnson's Rybrevant is approved but still used with chemotherapy.

For ArriVent, the commercial implication is as important as the statistical one. Firmonertinib, described by the company as a brain-penetrant inhibitor of both classical and uncommon EGFR mutations, needed a clear phase 3 win to differentiate itself in EGFR exon 20 insertion-mutant non-small cell lung cancer. Instead, the dataset leaves ArriVent reassessing the development path.

The Data

The phase 3 study enrolled 398 people with non-squamous, locally advanced or metastatic NSCLC whose tumors had exon 20 insertion mutations. Participants received one of two doses of firmonertinib or platinum-based chemotherapy as a first-line treatment.

By BICR, median progression-free survival was 11 months on the high dose of firmonertinib versus 9.5 months in the control arm. The low dose performed numerically worse than control, with median PFS of 8.4 months. Because BICR was the basis for the primary endpoint, those results drove the trial failure.

ArriVent highlighted a more favorable picture from investigator assessment, where median PFS was 11.1 months on the high dose and 7.1 months in the control cohort. But sponsors generally use BICR to reduce variability and bias, making it the more robust assessment.

Response rate data favored the high dose in both analyses. By BICR, the response rate was 60% on high-dose firmonertinib compared with 33% in the control arm. Even so, the PFS miss dominated investor reaction.

ArriVent also reported "a trend toward an improvement" in overall survival, but said the data are not yet mature. The safety profile was consistent with earlier trials of firmonertinib.

Why The Readout Landed Poorly

The control arm appears to be part of the problem. Guggenheim Securities analysts said back in April that Johnson & Johnson, ArriVent and other sponsors of recent phase 3 trials in the setting had assumed median PFS of five to seven months in the control arm. In Furvent, the control arm reached 9.5 months by BICR.

That made outperformance harder to show. Johnson & Johnson's phase 3 trial reported median PFS of 11.4 months for Rybrevant plus chemotherapy versus 6.7 months in the control arm, setting a much clearer benchmark for superiority. Guggenheim had predicted ArriVent shares could rise $40 if Furvent delivered data at least comparable to the Rybrevant trial; instead, the stock opened at $12.37, down about $16.

CEO Bing Yao said ArriVent is evaluating the dataset to determine the "most appropriate development path for firmonertinib." That leaves the program in a narrower position: without the planned phase 3 differentiation, any future case for the drug may depend more heavily on subgroup interpretation, later survival data or a different development strategy than the straightforward first-line, chemotherapy-free path Furvent was meant to establish.