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)
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.
Arms & interventions
- DrugFirmonertinib
240 mg oral, daily firmonertinib tablet
- DrugEGFR-TKI inhibitor based on investigator's choice
osimertinib 80 mg oral, daily tablet OR afatinib 40 mg oral, daily tablet
Outcome measures
Primary
Progression Free Survival (PFS) determined by blinded independent central review (BICR)
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.
Time frame: Until progression or death, assessed up to approximately 4 years
Confirmed overall response rate (ORR) as determined by BICR
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.
Time frame: Until progression or death, assessed up to approximately 3 years
Secondary
Overall survival (OS)
Time frame: Until death, assessed up to approximately 5 years
Investigator-assessed PFS
Time frame: Until progression or death, assessed up to approximately 4 years
Investigator-assessed confirmed ORR
Time frame: Until progression or death, assessed up to approximately 3 years
Duration of response (DOR)
Time frame: Until progression or death, assessed up to approximately 4 years
Time to second Progression-free survival (PFS2)
Time frame: Assessed up to approximately 5 years
Incidence and severity of adverse events (AEs), as a measure of safety and tolerability of firmonertinib
Time frame: Assessed up to approximately 5 years
Change from baseline in safety-related clinical laboratory test results
Time frame: Assessed up to approximately 5 years
Eligibility criteria
Study locations (16)
USC/Norris Comprehensive Cancer Center
Los Angeles, California, 90033
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
UCSF Medical Center-Mission Bay
San Francisco, California, 94158
Kaiser Permanente Medical Center
Vallejo, California, 94589
Illinois Cancer Specialists
Arlington Heights, Illinois, 60005
University of Illinois Hospital and Health Sciences Systems
Chicago, Illinois, 60612
Northwell Health/R.J. Zuckerberg Cancer Center
Lake Success, New York, 11042
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
New York, New York, 10016
Ohio State University Hospitals
Columbus, Ohio, 43210
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Texas Oncology
Dallas, Texas, 75246
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
University of Virginia
Charlottesville, Virginia, 22903
Virginia Cancer Specialists
Fairfax, Virginia, 22031
Shenandoah Oncology, P.C.
Winchester, Virginia, 22601
Swedish Cancer Institute
Edmonds, Washington, 98026