ArriVent’s Firmonertinib Fails Primary PFS Endpoint Despite Higher ORR in FURVENT

ArriVent BioPharma announced results from the global, pivotal Phase 3 FURVENT trial (NCT05607550), evaluating firmonertinib monotherapy in patients with previously untreated, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations.

The three-arm study enrolled 398 patients across the United States, Europe, Japan, China, and other participating regions. Patients received once-daily firmonertinib at 160 mg or 240 mg, or platinum-based chemotherapy with pemetrexed as the control treatment.

The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review (BICR) according to RECIST 1.1. Secondary endpoints included overall survival (OS), investigator-assessed PFS, confirmed objective response rate (ORR) by BICR, and central nervous system outcomes in patients with baseline brain metastases.

Primary PFS Endpoint Was Not Met

FURVENT did not meet its primary endpoint of BICR-assessed PFS.

For patients receiving firmonertinib 240 mg, median BICR-assessed PFS was 11.0 months compared with 9.5 months in the control arm. The hazard ratio (HR) was 0.75 (95% confidence interval [CI], 0.55–1.02), with a p-value of 0.0654.

The HR of 0.75 corresponds to a numerical 25% relative reduction in the risk of disease progression or death compared with chemotherapy. However, the 95% CI crossed 1.0 and the p-value was above the conventional 0.05 threshold, meaning the primary PFS analysis did not demonstrate statistical significance.

In the 160 mg arm, median BICR-assessed PFS was 8.4 months compared with 9.5 months with control, with an HR of 0.91 (95% CI, 0.67–1.25).

Thus, while the 240 mg dose showed a numerical improvement in median BICR-assessed PFS, the trial did not achieve its primary endpoint.

Investigator-Assessed PFS Favored Firmonertinib 240 mg

The investigator-assessed PFS analysis showed a more favorable result for the 240 mg dose.

Median investigator-assessed PFS was 11.1 months with firmonertinib 240 mg versus 7.1 months with control, corresponding to an HR of 0.61 (95% CI, 0.46–0.81).

For firmonertinib 160 mg, median investigator-assessed PFS was 8.3 months, with an HR of 0.86 (95% CI, 0.65–1.14) versus control.

Although these findings favored firmonertinib 240 mg, investigator-assessed PFS was a secondary endpoint. Therefore, the result does not alter the primary BICR-assessed PFS outcome.

Confirmed Objective Response Rate Was Higher with Firmonertinib 240 mg

Confirmed ORR also favored firmonertinib, particularly at the 240 mg dose.

According to BICR assessment, confirmed ORR was:

• 60% with firmonertinib 240 mg
• 35% with firmonertinib 160 mg
• 33% with control

By investigator assessment, confirmed ORR was:

• 61% with firmonertinib 240 mg
• 41% with firmonertinib 160 mg
• 28% with control

These findings demonstrate antitumor activity with firmonertinib, with the 240 mg dose producing the highest confirmed response rate among the three treatment groups. However, ORR was a secondary efficacy measure and does not change the outcome of the primary PFS analysis.

Overall Survival Analysis Remains Immature

Overall survival was included as a secondary endpoint in FURVENT. ArriVent reported a trend toward improvement in overall survival, but the analysis was not yet mature.

The company is evaluating the full FURVENT dataset as it considers the most appropriate development path for firmonertinib in first-line EGFR exon 20 insertion-mutant NSCLC.

 Safety Profile Remained Consistent with Previous Studies

The safety profile observed in FURVENT was consistent with previous clinical studies of firmonertinib, and no new safety signals were identified.

Grade ≥3 treatment-emergent adverse events occurred in:

Treatment	Grade ≥3 TEAEs
Firmonertinib 240 mg	52%
Firmonertinib 160 mg	53%
Control	55%

Grade ≥3 treatment-related adverse events occurred in:

Treatment	Grade ≥3 TRAEs
Firmonertinib 240 mg	26%
Firmonertinib 160 mg	22%
Control	40%

The reported safety findings did not identify a new safety concern associated with firmonertinib in the FURVENT population.

Firmonertinib Development Program

Firmonertinib is an oral, highly brain-penetrant, mutation-selective EGFR inhibitor with activity against classical and uncommon EGFR mutations, including EGFR exon 20 insertion mutations.

The drug is approved in China for first-line advanced NSCLC with EGFR exon 19 deletion or L858R mutations, as well as previously treated locally advanced or metastatic NSCLC with EGFR T790M mutations. It is also approved for patients with EGFR exon 20 insertion mutations whose disease has progressed during or after platinum-containing chemotherapy or who are intolerant to platinum-containing chemotherapy.

Firmonertinib has received U.S. FDA Breakthrough Therapy Designation for previously untreated, locally advanced or metastatic non-squamous NSCLC with EGFR exon 20 insertion mutations. It has also received Orphan Drug Designation for NSCLC with EGFR, HER2, or HER4 mutations.

Beyond FURVENT, firmonertinib is being evaluated in the global Phase 3 ALPACCA trial (NCT07185997) in first-line NSCLC patients with EGFR PACC mutations.

What the FURVENT Results Mean

The FURVENT results present a mixed efficacy picture for firmonertinib in first-line EGFR exon 20 insertion-mutant NSCLC.

The 240 mg dose produced a numerical improvement in BICR-assessed median PFS, with 11.0 months versus 9.5 months for chemotherapy. It also produced higher confirmed ORR and a more favorable investigator-assessed PFS result.

However, the primary BICR-assessed PFS endpoint was not met. The HR of 0.75 had a 95% CI that crossed 1.0, and the p-value of 0.0654 did not meet the conventional threshold for statistical significance.

The immature overall survival analysis means that the full clinical benefit of firmonertinib cannot yet be determined from the available data. ArriVent’s further assessment of the complete FURVENT dataset will therefore be important in determining the future development strategy for the drug in this patient population.

Reference

ArriVent Announces Program Update from the Phase 3 FURVENT Trial of Firmonertinib in First-Line EGFR Exon 20 Insertion Mutant NSCLC, ArriVent BioPharma, October 6, 2026.

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 ID NCT05607550