Firmonertinib Misses PFS End Point in EGFR Exon 20–Mutant NSCLC

Firmonertinib did not significantly improve progression-free survival (PFS) by blinded independent central review (BICR) over platinum-based chemotherapy in patients with untreated, advanced nonsquamous non–small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion mutations, according to topline results from the phase 3 FURVENT trial (NCT05607550).¹

The higher firmonertinib dose explored in the trial did show activity on secondary end points, including investigator-assessed PFS and confirmed objective response rate (ORR) by BICR. Immature overall survival (OS) data also trended in favor of firmonertinib, and no new safety signals emerged.¹

By BICR, patients assigned to firmonertinib 240 mg achieved a median PFS of 11.0 months compared with 9.5 months for those given chemotherapy (HR, 0.75; 95% CI, 0.55-1.02; P = .0654). The 160-mg dose produced a median PFS of 8.4 months by BICR (HR vs control, 0.91; 95% CI, 0.67-1.25).¹

“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," Bing Yao, PhD, chairman and chief executive officer of ArriVent, stated in a 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. We are deeply grateful to the patients, investigators and clinical teams who made this program possible and are evaluating the full FURVENT dataset as we determine the most appropriate development path for firmonertinib.”¹

The gap between arms was wider under investigator assessment. Median PFS reached 11.1 months with firmonertinib 240 mg vs 7.1 months with chemotherapy (HR, 0.61; 95% CI, 0.46-0.81). With the 160-mg dose, investigator-assessed median PFS was 8.3 months (HR vs control, 0.86; 95% CI, 0.65-1.14).¹

Response data followed a similar dose-dependent pattern. The confirmed ORR by BICR was 60% in the 240-mg arm, 35% in the 160-mg arm, and 33% in the chemotherapy arm. Per investigator assessment, confirmed ORRs were 61%, 41%, and 28%, respectively.¹

The 240-mg frontline dose was informed by the phase 1b FAVOUR study (NCT04858958). In data presented at the 2023 World Conference on Lung Cancer, treatment-naive patients with EGFR exon 20 insertion-mutant NSCLC who received firmonertinib 240 mg daily (n = 30) achieved a confirmed ORR of 78.6% (95% CI, 59.05%-91.70%) by independent review. All responses were partial (n = 22), and the remaining 6 evaluable patients had stable disease, yielding a disease control rate of 100% (95% CI, 87.66%-100.00%). The median duration of response was 15.2 months (95% CI, 8.74-24.84), and median maximum tumor shrinkage was 50.9%.²

Is Firmonertinib Better Tolerated Than Chemotherapy?

Grade 3 or higher treatment-emergent adverse events occurred in 52% of patients in the 240-mg arm, 53% of those in the 160-mg arm, and 55% of patients receiving chemotherapy. Grade 3 or higher treatment-related adverse events (TRAEs) were less common with firmonertinib, at 26% and 22% for the 240-mg and 160-mg doses, respectively, vs 40% with chemotherapy.¹

In the FAVOUR frontline 240-mg cohort, most TRAEs were grade 1 or 2, low-grade diarrhea was most common, and no patient discontinued because of a TRAE.²^,³

How FURVENT Tested 2 Firmonertinib Doses Against Chemotherapy

The global, randomized, 3-arm FURVENT trial together enrolled 398 patients with previously untreated, locally advanced or metastatic non-squamous NSCLC with EGFR exon 20 insertion mutations at sites across the United States, Europe, and Asia, including Japan and China. Patients received oral firmonertinib at 160 mg or 240 mg once daily. Each dose was compared against the standard first-line regimen of pemetrexed plus platinum-based chemotherapy.¹

PFS by BICR per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 served as the primary end point. Secondary end points included OS, investigator-assessed PFS, and confirmed ORR by BICR. Among patients with baseline brain metastases, investigators also evaluated central nervous system (CNS) ORR and CNS PFS using modified RECIST.¹

Where Firmonertinib Stands in EGFR-Mutant NSCLC

Firmonertinib is a highly brain-penetrant, mutation-selective EGFR inhibitor with activity against classical and uncommon EGFR alterations, including exon 20 insertions and P-loop αC-helix compressing (PACC) mutations. In China, it is approved for 3 uses:

• first-line treatment of advanced NSCLC with EGFR exon 19 deletions or L858R mutations
• previously treated disease with EGFR T790M mutations
• exon 20 insertion-mutant disease that has progressed on or after platinum-based chemotherapy, or in patients who cannot tolerate it.¹

The FDA previously granted firmonertinib breakthrough therapy designation for the same first-line exon 20 insertion population studied in FURVENT. It also granted orphan drug designation for NSCLC with EGFR, HER2, or HER4 mutations. The drug is also being studied in the global phase 3 ALPACCA trial (NCT07185997) as first-line therapy for patients with EGFR PACC mutations.¹

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. October 6, 2026. Accessed October 6, 2026. https://tinyurl.com/5an7rcse

2. Allist and ArriVent announce interim results from ongoing phase 1b trial with furmonertinib at the 2023 World Conference on Lung Cancer. News release. ArriVent BioPharma; Allist Pharmaceuticals. September 2023. Accessed October 6, 2026. https://tinyurl.com/y7ryzy4x