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NCT Number: NCT07185997

Study to Evaluate Efficacy and Safety of Firmonertinib Compared With Investigator's Choice of EGFR Inhibitor as First-Line Treatment in Participants Who Have Locally Advanced or Metastatic NSCLC With EGFR P-Loop and Alpha C-Helix Compressing (PACC) Uncommon Mutations

Global, Phase 3, randomized, multicenter, open-label study evaluating the efficacy and safety of firmonertinib at a dose level of 240 mg QD compared to investigator's choice of osimertinib (80 mg QD) or afatinib (40 mg QD) in participants who have locally advanced or metastatic NSCLC with EGFR PACC mutations, and who have not received any prior therapy for advanced disease. Participants will be randomized in a 1:1 ratio to treatment with firmonertinib or osimertinib or afatinib and will take the assigned dose daily.

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Key information

Conditions

Non-Small-Cell Lung Cancer Advanced Non-Small-Cell Lung Cancer Bronchial Diseases Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung EGFR P-Loop and Alpha C-Helix Compressing EGFR PACC EGFR Uncommon Mutations Lung Diseases Lung Neoplasms Metastatic Non-Small-Cell Lung Cancer Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Blacktown Cancer and Haematology Centre, Blacktown, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Firmonertinib

Drug

240 mg oral, daily firmonertinib tablet

Other names: AST2818

EGFR-TKI inhibitor based on investigator's choice

Drug

osimertinib 80 mg oral, daily tablet OR afatinib 40 mg oral, daily tablet

Primary outcomes

  1. Progression Free Survival (PFS) determined by blinded independent central review (BICR)

    Time frame: Until progression or death, assessed up to approximately 4 years

    PFS is defined as the time from randomization to the first occurrence of disease progression as determined by BICR using RECIST v1.1, or death from any cause, whichever occurs first.

  2. Confirmed overall response rate (ORR) as determined by BICR

    Time frame: Until progression or death, assessed up to approximately 3 years

    Confirmed ORR is defined as the percentage of participants with a confirmed CR or PR based on BICR assessment relative to the total number of participants.

Secondary outcomes

  1. Overall survival (OS)

    Time frame: Until death, assessed up to approximately 5 years

    OS is defined as the time from randomization to death from any cause.

  2. Investigator-assessed PFS

    Time frame: Until progression or death, assessed up to approximately 4 years

    Investigator-assessed PFS is defined as the time from randomization to the first documented disease progression or death, whichever occurs first, based on investigator assessment per RECIST v1.1.

  3. Investigator-assessed confirmed ORR

    Time frame: Until progression or death, assessed up to approximately 3 years

    Investigator-assessed confirmed ORR is defined as the percentage of participants with a confirmed CR or PR based on investigator assessment relative to the total number of participants.

  4. Duration of response (DOR)

    Time frame: Until progression or death, assessed up to approximately 4 years

    DOR is defined as the time from first documented evidence of CR or PR until the first documented evidence of disease progression or death, whichever occurs first.

  5. Time to second Progression-free survival (PFS2)

    Time frame: Assessed up to approximately 5 years

    PFS2 is defined as the time from randomization to second progression (ie, earliest of the subsequent progression events after initiation of a new anti-cancer treatment), or death from any cause, whichever occurs first.

  6. Incidence and severity of adverse events (AEs), as a measure of safety and tolerability of firmonertinib

    Time frame: Assessed up to approximately 5 years

    An AE is defined as any unfavorable or unintended medical occurrence in a trial participant administered a pharmaceutical product, regardless of causal attribution.

  7. Change from baseline in safety-related clinical laboratory test results

    Time frame: Assessed up to approximately 5 years

    Safety-related laboratory parameters include absolute neutrophil count, hemoglobin, platelet count, albumin, blood urea nitrogen (BUN), chloride, creatinine, potassium, sodium, alkaline phosphatase (ALP), alanine aminotransferase (ALT); aspartate aminotransferase (AST), total bilirubin. Each parameter is measured using its standard unit. Changes in participants' laboratory test values are evaluated by comparing baseline (pre-treatment) results with those obtained at prespecified time points during or following the treatment.

Study contacts

Contact information is provided by the study sponsor or research team.

Vanessa Esquibel

CONTACT

[email protected]

619-540-3451

Sponsors and collaborators

Lead sponsor

ArriVent BioPharma, Inc.

Industry

Registry information

Official study title

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)

Important dates

Study start
2025
Primary completion
2029
Study completion
2030
First posted
Sep 22, 2025
Registry last updated
Jul 2, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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