Sponsor: ArriVent BioPharma, Inc. (industry)
Phase: 3
Start date: Sept. 22, 2025
Planned enrollment: 480
Firmonertinib (also called furmonertinib, AST-2818 or ASK-120067) is an oral drug studied mainly for EGFR-mutated non-small-cell lung cancer (NSCLC). It has been evaluated in human trials, including a completed randomized phase 3 trial for common EGFR mutations. Separate phase 3 trials are evaluating it for EGFR exon 20 insertions and uncommon PACC mutations; the cited trial descriptions do not report outcomes from those trials. (pubmed.ncbi.nlm.nih.gov)
Firmonertinib is an irreversible EGFR tyrosine-kinase inhibitor designed to inhibit mutant EGFR, including common activating mutations, the T790M resistance mutation and certain exon 20 insertions. Blocking EGFR kinase activity is intended to interrupt signals that drive tumor growth. (aacrjournals.org)
In FURLONG, grade 3 or higher treatment-related adverse events occurred in 11% of firmonertinib recipients versus 18% of gefitinib recipients. Reported adverse effects across firmonertinib studies include diarrhea, rash and liver-enzyme elevations; less common but potentially serious effects warrant attention as larger studies mature. Safety findings at one dose or in one patient group should not be assumed to apply unchanged to another. (pubmed.ncbi.nlm.nih.gov)
Last updated: Sep 2026
Goal: Determine whether first-line firmonertinib improves outcomes compared with investigator-selected osimertinib or afatinib in advanced NSCLC with uncommon EGFR PACC mutations.
Patients: Participants have locally advanced or metastatic NSCLC with a documented EGFR PACC mutation and have received no systemic therapy for advanced disease. Asymptomatic CNS metastases are permitted. Prior perioperative treatment is allowed if the treatment-free interval is at least 12 months.
Design: Global, multicenter, open-label trial with 1:1 randomization to firmonertinib or the investigator’s choice of comparator.
Treatments: Participants take oral firmonertinib 240 mg once daily or oral osimertinib 80 mg once daily or afatinib 40 mg once daily. Firmonertinib is an irreversible EGFR tyrosine kinase inhibitor intended to block mutant EGFR signaling. Earlier studies reported a 68.2% confirmed response rate in a small PACC-mutation cohort and longer progression-free survival than gefitinib in patients with common EGFR mutations; neither result establishes benefit over the comparators in this trial. Osimertinib and afatinib are EGFR tyrosine kinase inhibitors used as active comparators.
Outcomes: The primary endpoints are blinded independent central review–assessed progression-free survival by RECIST v1.1 and confirmed overall response rate. Secondary endpoints include overall survival, investigator-assessed progression-free survival and response rate, duration of response, time to second progression, adverse events, and changes in safety laboratory results.
Burden on patient: Expected burden is moderate: treatment is oral and once daily, but participants will need repeated visits for tumor assessments, safety laboratory tests, and adverse-event monitoring, potentially over several years. The provided information does not specify visit or scan frequency or require research biopsies or intensive pharmacokinetic sampling.
Last updated: Sep 2026
Key Eligibility Criteria:
* Histologically or cytologically documented, locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) not amenable to curative surgery or radiotherapy.
* Documented results of the presence of an Epidermal Growth Factor Receptor (EGFR) PACC mutation in tumor tissue or blood from local testing.
* No prior systemic anticancer therapy regimens received for locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) including prior treatment with any Epidermal Growth Factor Receptor (EGFR)-targeting agents (e.g., previous (EGFR) TKIs, monoclonal antibodies, or bispecific antibodies).
* Patients who have received prior neo-adjuvant and/or adjuvant chemotherapy, immunotherapy, or chemo radiotherapy for non-metastatic disease must have experienced a treatment free interval of at least 12 months.
* Patients with asymptomatic CNS metastases are eligible.
Blacktown, New South Wales, 2148, Australia
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St Leonards, New South Wales, 2065, Australia
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Heidelberg, Victoria, 3084, Australia
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Taichung, 407219, Taiwan
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Vallejo, California, 94589, United States
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Arlington Heights, Illinois, 60005, United States
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Winchester, Virginia, 22601, United States
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Charlottesville, Virginia, 22903, United States
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Fairfax, Virginia, 22031, United States
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