Firmonertinib Misses PFS End Point in First-Line EGFR Exon 20 NSCLC

The phase 3 FURVENT trial (NCT05607550) evaluating firmonertinib monotherapy in patients with previously untreated, locally advanced or metastatic nonsquamous non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations did not meet its primary end point of progression-free survival (PFS) by blinded independent central review (BICR), according to a news release from the developer, ArriVent BioPharma.¹ Clinical benefit was observed in secondary end points, including PFS by investigator assessment and confirmed objective response rate (ORR) by BICR, and an immature trend toward improved overall survival (OS) was also reported.

What were the key efficacy results?

By BICR, the median PFS was 11.0 months with firmonertinib at 240 mg, 8.4 months with firmonertinib at 160 mg, and 9.5 months with control chemotherapy; the comparison of the 240-mg dose vs control did not reach statistical significance (HR, 0.75; 95% CI, 0.55-1.02; P = .0654), and the 160-mg dose showed an HR of 0.91 (95% CI, 0.67-1.25) vs control. The confirmed ORR by BICR was 60% with firmonertinib at 240 mg, 35% at 160 mg, and 33% with control.

By investigator assessment, the median PFS was 11.1 months at 240 mg, 8.3 months at 160 mg, and 7.1 months with control, with an HR of 0.61 (95% CI, 0.46-0.81) for the 240-mg dose vs control and 0.86 (95% CI, 0.65-1.14) for the 160-mg dose. The corresponding investigator-assessed ORRs were 61%, 41%, and 28%.

“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,” said Bing Yao, PhD, chairman and chief executive officer of ArriVent, in the news release.¹ “While the safety profile observed with firmonertinib was consistent with previous clinical studies, FURVENT did not show a meaningful improvement in PFS over chemotherapy by BICR in this study.”

What was the safety profile of firmonertinib?

The safety profile observed in FURVENT was consistent with previous clinical studies of firmonertinib, with no new safety signals identified. Grade 3 or higher treatment-emergent adverse events occurred in 52% of patients receiving firmonertinib at 240 mg, 53% receiving firmonertinib at 160 mg, and 55% in the control arm. Grade 3 or higher treatment-related adverse events occurred in 26%, 22%, and 40% of patients, respectively.

What is the FURVENT trial design?

FURVENT is a global, pivotal, 3-arm phase 3 trial evaluating patients with first-line nonsquamous locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. The trial assessed firmonertinib administered at either 160 mg or 240 mg once daily, with each dose compared with platinum-based chemotherapy plus pemetrexed, the current first-line standard of care.

The primary end point was PFS by BICR per RECIST v1.1 criteria. Secondary end points included OS, PFS by investigator assessment, confirmed ORR by BICR, and central nervous system (CNS) overall response rate and CNS-PFS by modified RECIST criteria among patients with brain metastases at baseline.² The study enrolled 398 patients globally, including at sites in the US, Europe, and certain Asian countries including Japan and China.

What is firmonertinib, and what comes next?

Firmonertinib is an oral, highly brain-penetrant, mutation-selective EGFR inhibitor that is active against both classical and uncommon EGFR mutations, including PACC and exon 20 insertion mutations. It is approved in China for several indications, including first-line advanced NSCLC with EGFR exon 19 deletions or L858R mutations and EGFR exon 20 insertion mutation–positive NSCLC after progression on or intolerance to platinum-containing chemotherapy. The agent holds FDA breakthrough therapy designation for patients with previously untreated locally advanced or metastatic nonsquamous NSCLC with EGFR exon 20 insertion mutations, as well as orphan drug designation for NSCLC with EGFR, HER2, or HER4 mutations.

Developers stated that they are evaluating the full FURVENT dataset as they determine the most appropriate development path for firmonertinib. Firmonertinib is also being studied in the global phase 3 ALPACCA trial (NCT07185997) in first-line NSCLC with EGFR PACC mutations.

References

1. ArriVent announces program update from the phase 3 FURVENT trial of firmonertinib in first-line EGFR exon 20 insertion mutant NSCLC. News release. ArriVent BioPharma, Inc. October 6, 2026. Accessed October 6, 2026. https://tinyurl.com/52nez6ae
2. Study to compare furmonertinib to platinum-based chemotherapy for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations (FURVENT). ClinicalTrials.gov. Updated June 22, 2025. Accessed October 6, 2026. https://tinyurl.com/weneyjnj