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
- 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 Mutations
- Interventions
- Drug: FirmonertinibDrug: EGFR-TKI inhibitor based on investigator's choice
- Registration Number
- NCT07185997
- Lead Sponsor
- ArriVent BioPharma, Inc.
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 480
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Firmonertinib 240 mg Firmonertinib - EGFR-TKI inhibitor osimertinib or afatinib based on investigator's choice EGFR-TKI inhibitor based on investigator's choice -
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) determined by blinded independent central review (BICR) 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.
Confirmed overall response rate (ORR) as determined by BICR 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 Outcome Measures
Name Time Method Overall survival (OS) Until death, assessed up to approximately 5 years OS is defined as the time from randomization to death from any cause.
Investigator-assessed PFS 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.
Investigator-assessed confirmed ORR 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.
Duration of response (DOR) 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.
Time to second Progression-free survival (PFS2) 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.
Incidence and severity of adverse events (AEs), as a measure of safety and tolerability of firmonertinib 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.
Change from baseline in safety-related clinical laboratory test results 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.