A phase 3 lung cancer study of ArriVent BioPharma’s EGFR inhibitor has missed its primary endpoint, sending the biotech’s stock down 57% in early trading.
The study enrolled 398 people with non-squamous locally advanced or metastatic non-small cell lung cancer (NSCLC). Participants, all of whom had exon 20 insertion mutations, received one of two doses of ArriVent's firmonertinib or platinum-based chemotherapy as a first-line treatment. Johnson & Johnson’s Rybrevant is approved in the setting, but patients still receive chemotherapy with the bispecific antibody.
ArriVent’s phase 3 Furvent trial could have positioned firmonertinib, a brain-penetrant inhibitor of both classical and uncommon EGFR mutations, as a chemotherapy-free treatment option. However, the data disappointed ArriVent.
Furvent missed its primary endpoint of progression-free survival (PFS) by blinded independent central review (BICR). Median PFS on the high dose of firmonertinib was 11 months, compared to 9.5 months in the control arm. The low dose of firmonertinib performed numerically worse than the control therapy, achieving a median PFS of 8.4 months.
ArriVent acknowledged that the data fell short of its expectations, although it also noted some positives. The PFS data were stronger when evaluated by investigator’s assessment rather than BICR, with 11.1 months on the high dose playing off against 7.1 months in the control cohort.
Sponsors use BICR to limit variability and bias, typically making it the more robust assessment. But the investigator’s assessment delivered control group data closer to analyst expectations. J&J, ArriVent and the other three sponsors of recent phase 3 trials in the setting all assumed median PFS of five to seven months in the control arm, Guggenheim Securities analysts said in a note to investors back in April.
J&J’s phase 3 trial reported (PDF) a median PFS of 11.4 months in patients who received Rybrevant plus chemotherapy, compared to 6.7 months in the control arm. Guggenheim analysts predicted that ArriVent shares could rise $40 if Furvent data were at least comparable to the Rybrevant trial. Instead, ArriVent’s stock opened down 57% at $12.37, wiping about $16 off the share price.
The response rate favored the high dose of firmonertinib over the control in both analyses. By BICR, the response rate on the high dose of firmonertinib was 60%, compared to 33%. However, the PFS failure overshadowed the response rate data.
Positive overall survival (OS) data could, in turn, override the PFS miss. But, with the data yet to mature, ArriVent only reported “a trend toward an improvement” in OS.
The biotech is evaluating the dataset to inform the “most appropriate development path for firmonertinib,” ArriVent CEO Bing Yao, Ph.D., said in a statement. The safety profile was consistent with earlier trials of firmonertinib.
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