Frontline Firmonertinib Generates Durable Efficacy in EGFR PACC–Mutant NSCLC

Non–Small Cell Lung Cancer |
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First-line treatment with the EGFR inhibitor firmonertinib (formerly furmonertinib) led to durable efficacy in patients with non–small cell lung cancer (NSCLC) harboring EGFR PACC mutations, according to updated data from the phase 1b FURTHER trial (NCT05364073).1

Findings announced by ArriVent BioPharma showed that at a median follow-up of 12.5 months, patients treated with firmonertinib at a dose of 240 mg experienced a median progression-free survival (PFS) of 16.0 months per blinded independent central review.

At dose levels of 240 mg and 160 mg, the respective overall response rates (ORRs) were 68.2% and 43.5%. At the 240-mg dose, the median duration of response was 14.6 months. Responses were observed at the first tumor assessment in the majority of patients, and most patients treated at the 240-mg dose remained on the study after 1 year.

Notably, in evaluable patients (n = 17), the confirmed central nervous system (CNS) ORR was 53%, and the confirmed CNS complete response rate was 41%.

Regarding safety, the agent was well tolerated and had a profile consistent with EGFR inhibitors. The most common treatment-related adverse effects (AEs) comprised diarrhea, elevated hepatic enzyme levels, rash, stomatitis, and dry skin.

“We are encouraged by the strong PFS and durable systemic responses with long-term firmonertinib treatment in [patients with] frontline EGFR PACC–mutant NSCLC. Moreover, the generally well-tolerated safety profile is consistent with what has been clinically established,” Bing Yao, PhD, chairman and chief executive officer of ArriVent BioPharma, stated in a news release. “We believe these phase 1b findings support the advancement of firmonertinib towards a registration study for EGFR PACC–mutant NSCLC, with potential for accelerated approval. We expect to enroll the first patient in the second half of 2025 in our randomized, global pivotal [phase 3] ALPACCA trial.”

Diving FURTHER into the Study Design

FURTHER was an open-label, multi-center, dose-escalation and dose-expansion study evaluating firmonertinib in patients with advanced or metastatic NSCLC harboring EGFR or HER2 mutations.2 Patients needed to be at least 18 years of age with histologically or cytologically documented, locally advanced or metastatic NSCLC not amenable for curative surgery or radiotherapy.

The study included cohorts of patients with previously treated disease; however, cohort 4 in stage 2 was dedicated to patients with previously untreated or TKI-naive NSCLC harboring uncommon EGFR mutations, excluding exon 20 insertion mutations.

Patients were excluded from cohort 4 of stage 2 if they experienced disease progression during neoadjuvant or adjuvant therapy, or within 12 months of completing those regimens. Key exclusion criteria for all patients included receipt of other systemic anticancer therapy within 3 weeks of treatment; anticancer radiation therapy within 4 weeks of the first study dose; palliative radiation for bone metastases within 2 weeks of enrollment; and lack of resolution of AEs from prior therapies.

All patients received firmonertinib once per day.1,2 Notably, the 240-mg dose was selected as the optimal dose for the phase 3 study.1

PFS served as the primary end point for FURTHER. Secondary end points included overall survival, safety, patient-reported outcomes, and pharmacokinetics.

“Patients with [EGFR] PACC–mutant NSCLC represent an underserved population,” Stuart Lutzker, MD, PhD, co-founder and president of R&D at ArriVent, added in the news release. “We believe the interim median PFS of 16.0 months observed in the FURTHER study is clinically meaningful, and together with the compelling CNS activity and favorable safety profile underscore the potential of firmonertinib to address unmet needs across patients with [EGFR] PACC mutations as a once-daily oral, chemo-free monotherapy.”

References

1. ArriVent announces positive interim firmonertinib monotherapy data from global phase 1b study in EGFR PACC mutant non-small cell lung cancer and plans to advance into a global pivotal study. News release. ArriVent BioPharma. June 23, 2025. Accessed Jun 25, 2025. https://ir.arrivent.com/news-releases/news-release-details/arrivent-announces-positive-interim-firmonertinib-monotherapy
2. Study of furmonertinib in patients with advanced or metastatic non-small cell lung cancer (NSCLC) with activating, including uncommon, epidermal growth factor receptor (EGFR) or human epidermal growth factor receptor 2 (HER2) mutations. ClinicalTrials.gov. Updated May 1, 2025. Accessed June 25, 2025. https://www.clinicaltrials.gov/study/NCT05364073