Firmonertinib Fails to Meet PFS End Point in First-Line EGFR Exon 20 Insertion–Mutant NSCLC

First-line firmonertinib did not significantly improve progression-free survival (PFS) by blinded independent central review (BICR) vs platinum-based chemotherapy plus pemetrexed in patients with locally advanced or metastatic nonsquamous non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations, missing the primary end point of the phase 3 FURVENT trial (NCT05607550).¹

The median BICR-assessed PFS was 11.0 months with firmonertinib at 240 mg once daily vs 9.5 months with control (HR, 0.75; 95% CI, 0.55-1.02; P = .0654). In the 160-mg arm, the median PFS by BICR was 8.4 months (HR vs control, 0.91; 95% CI, 0.67-1.25).

“These disappointing results are not what we hoped for,” Bing Yao, PhD, stated in a news release. Yao is chairman and chief executive officer of ArriVent BioPharma.

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

What was the design of the phase 3 FURVENT trial of firmonertinib in EGFR exon 20 insertion–mutant NSCLC?

FURVENT is a global, randomized, open-label, 3-arm trial that enrolled 398 patients in the United States (US), Europe, and Asia, including Japan and China.^1,2 Eligible patients had locally advanced or metastatic nonsquamous NSCLC not amenable to curative surgery or radiotherapy, a documented EGFR exon 20 insertion mutation in tumor tissue or blood, and no prior systemic therapy for advanced disease, including EGFR-targeted agents.² Patients with treated or new asymptomatic central nervous system (CNS) metastases were eligible.

Patients were randomly assigned 1:1:1 to receive firmonertinib at 240 mg or 160 mg orally once daily or carboplatin or cisplatin in combination with pemetrexed.^1,2 The primary end point was PFS by BICR per RECIST 1.1 criteria. Secondary end points included overall survival (OS), investigator-assessed PFS, confirmed objective response rate (ORR) by BICR, and CNS ORR and CNS PFS in patients with baseline brain metastases.^1,2

What were the secondary efficacy outcomes with firmonertinib in the FURVENT trial?

The confirmed ORR by BICR was 60% among patients in the 240-mg arm, 35% among those in the 160-mg arm, and 33% among those in the control arm.

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

The OS data were immature at the time of the analysis, however, investigators observed a trend toward improved OS with firmonertinib.

What was the safety profile of firmonertinib in the FURVENT trial?

Grade 3 or higher treatment-emergent adverse effects (AEs) occurred in 52% of patients in the 240-mg arm, 53% of those in the 160-mg arm, and 55% of those in the control arm. Grade 3 or higher treatment-related AEs occurred in 26%, 22%, and 40% of patients, respectively. The safety profile of firmonertinib observed in FURVENT was deemed consistent with findings from prior clinical studies of the agent, and the investigators identified no new safety signals.

What is the global regulatory status of firmonertinib?

In the US, the agent holds breakthrough therapy designation for the treatment of previously untreated patients with locally advanced or metastatic nonsquamous NSCLC with EGFR exon 20 insertion mutations, as well as orphan drug designation for the treatment of patients with NSCLC with EGFR, HER2, or HER4 mutations.

In China, firmonertinib is approved for the first-line treatment of patients with advanced NSCLC with EGFR exon 19 deletions or L858R mutations, for the treatment of patients with previously treated NSCLC with EGFR T790M mutations, and for the treatment of patients with EGFR exon 20 insertion–mutant NSCLC following progression on or intolerance to platinum-based chemotherapy.

Additionally, the global phase 3 ALPACCA trial (NCT07185997) is evaluating firmonertinib for the first-line management of NSCLC harboring EGFR PACC mutations.

References

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://ir.arrivent.com/news-releases/news-release-details/arrivent-announces-program-update-phase-3-furvent-trial

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. Accessed October 6, 2026. https://clinicaltrials.gov/study/NCT05607550