ArriVent BioPharma has announced that its FURVENT Phase 3 trial evaluating firmonertinib monotherapy in previously untreated patients with locally advanced or metastatic non-squamous Non-Small Cell Lung Cancer (NSCLC) harbouring EGFR exon 20 insertion mutations did not meet its primary endpoint of Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR).

The global Phase 3 trial evaluated firmonertinib at doses of 160 mg and 240 mg once daily against platinum-based chemotherapy with pemetrexed, the current first-line standard of care. While the primary PFS endpoint was not met, clinical benefit was observed in secondary endpoints, including PFS assessed by investigators and confirmed objective response rate by BICR. A trend toward improved Overall Survival (OS) was also observed, although the data were not yet mature.

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

FURVENT is a global, three-arm Phase 3 study being conducted jointly by ArriVent and its partner Allist. The trial enrolled 398 patients across sites in the United States, Europe and selected Asian countries, including Japan and China.

The primary endpoint was PFS assessed by BICR according to RECIST 1.1. Secondary endpoints included OS, investigator-assessed PFS and confirmed objective response rate by BICR. In patients with brain metastases at baseline, the study also evaluated brain-specific central nervous system overall response rate and CNS-PFS using modified RECIST criteria.

Bing Yao, Ph.D., Chairman and Chief Executive Officer of ArriVent, said the company was disappointed by the FURVENT results and acknowledged the unmet need for more effective treatment options for patients with EGFR exon 20 insertion-mutant NSCLC. The company said it is evaluating the full dataset to determine the future development path for firmonertinib.

Firmonertinib is an oral, brain-penetrant, mutation-selective epidermal growth factor receptor (EGFR) inhibitor designed to target classical and uncommon EGFR mutations, including EGFR exon 20 insertion and PACC mutations. The drug is approved in China for certain patients with EGFR-mutated advanced NSCLC, including patients with EGFR exon 19 deletion or L858R mutations, T790M mutations and exon 20 insertion mutations following platinum-based chemotherapy or in patients who are intolerant to platinum-containing chemotherapy.

In the United States, firmonertinib has received FDA Breakthrough Therapy Designation for previously untreated patients with locally advanced or metastatic non-squamous NSCLC harbouring EGFR exon 20 insertion mutations. It has also received FDA Orphan Drug Designation for NSCLC with EGFR, HER2 or HER4 mutations.

Firmonertinib is also being evaluated in the global Phase 3 ALPACCA study in first-line NSCLC patients with EGFR PACC mutations.

Lung cancer remains the leading cause of cancer-related deaths globally, while NSCLC accounts for approximately 85 percent of lung cancer cases. EGFR exon 20 insertion mutations are uncommon EGFR alterations and account for approximately 9 percent of EGFR mutations. PACC mutations represent another uncommon group, accounting for approximately 12 percent of EGFR mutations. Patients with NSCLC harbouring uncommon EGFR mutations continue to face significant treatment challenges and unmet medical needs.