Advanced Non-Small-Cell Lung Cancer, EGFR PACC, EGFR P-Loop and Alpha C-Helix Compressing, EGFR Uncommon Mutations, Metastatic Non-Small-Cell Lung Cancer, Non-Small-Cell Lung Cancer
Conditions
Keywords
Non-Small Cell Lung Cancer (NSCLC), PACC, Firmonertinib, Furmonertinib, AST2818, FURMO-006, Drug-Therapy, Metastatic Non-Small Cell Lung Cancer, Advanced Non-Small Cell Lung Cancer, NSCLC, Osimertinib, Afatinib, metastatic NSCLC first-line treatment, Carcinoma NSCLC, Respiratory tract neoplasms, Bronchial Neoplasms, Protein Kinase Inhibitors, tyrosine kinase inhibitor (TKI), Alflutinib, Lung neoplasms, EGFR, EGFR kinase domain mutations, EGFR activating mutation, EGFR mutation of unknown significance, Non-classical EGFR mutation, EGFR uncommon mutations, EGFR atypical mutations, G719X, S768I, E709X, E709_T710delinsD, G779F, L747X, V774M, L747P/S, R776C/H, G724S, E736K, I740_K745dup, N771G, K757M/R, V769L/M
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.
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
Sponsors
ArriVent BioPharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Australia, Canada, China, France, Greece, Hong Kong, Italy, Japan, Malaysia, Singapore, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTClinical Trials
STUDY_DIRECTORJamuna Thimmarayappa
ArriVent BioPharm
Outcome results
None listed