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Firmonertinib versus standard EGFR drugs as first treatment for advanced NSCLC with EGFR PACC mutations

A Global, Phase 3, Randomized, Multicenter, Open-Label Study to Evaluate the Efficacy and Safety of Firmonertinib Compared With Investigator's Choice of Osimertinib or Afatinib as First-Line Treatment in Participants Who Have Locally Advanced or Metastatic Non-Small-Cell Lung Cancer With Epidermal Growth Factor Receptor P-Loop and Alpha C-Helix Compressing (PACC) Uncommon Mutations (ALPACCA)

Phase 3 Interventional ArriVent BioPharma, Inc. · NCT07185997

This trial tests whether daily firmonertinib works better than standard EGFR drugs (osimertinib or afatinib) as the first treatment for people with advanced NSCLC that has EGFR PACC mutations.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment480 (estimated)
Ages18 Years and up
SexAll
SponsorArriVent BioPharma, Inc. Industry-sponsored
Drugs / interventionschemotherapy, immunotherapy, firmonertinib, osimertinib, afatinib
Locations62 sites (Los Angeles, California and 61 other locations)
Trial IDNCT07185997 on ClinicalTrials.gov

What this trial studies

This global, randomized, multicenter, open-label Phase 3 trial assigns participants 1:1 to oral firmonertinib 240 mg once daily or investigator's choice of osimertinib 80 mg once daily or afatinib 40 mg once daily as first-line therapy for locally advanced or metastatic NSCLC with documented EGFR PACC mutations. Eligible participants must be treatment-naive for advanced disease, with prior adjuvant or neoadjuvant therapy allowed only if a treatment-free interval of at least 12 months has passed. Asymptomatic CNS metastases are permitted and patients are followed for efficacy and safety endpoints including tumor response and progression-free survival. Local testing of tumor tissue or blood is used to confirm EGFR PACC mutation status and the open-label design means both patients and investigators know the assigned treatment.

Who should consider this trial

Good fit: Adults with locally advanced or metastatic NSCLC who have a documented EGFR PACC mutation and have not received prior systemic therapy for advanced disease (prior adjuvant/neoadjuvant allowed if treatment-free ≥12 months) are the ideal candidates.

Not a fit: Patients without EGFR PACC mutations, those previously treated with EGFR-targeted therapy for advanced disease, or those with uncontrolled symptomatic brain metastases or poor organ function are unlikely to benefit.

Why it matters

Potential benefit: If successful, firmonertinib could provide better tumor control or longer progression-free survival than current EGFR inhibitor options for patients with EGFR PACC mutations.

How similar studies have performed: Some EGFR TKIs like osimertinib and afatinib have shown activity against certain uncommon EGFR mutations, but randomized phase 3 data specific to PACC mutations are limited and firmonertinib is a novel agent in this subgroup.

Eligibility criteria

Show full inclusion / exclusion criteria 
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.

Where this trial is running

Los Angeles, California and 61 other locations

+12 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Non-Small-Cell Lung CancerMetastatic Non-Small-Cell Lung CancerAdvanced Non-Small-Cell Lung CancerEGFR P-Loop and Alpha C-Helix CompressingEGFR PACCEGFR Uncommon MutationsNon-Small Cell Lung CancerPACC
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.