NIPH Clinical Trials Search

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

Basic Information

Recruitment status	Pending
Health condition(s) or Problem(s) studied	Non-Small-Cell Lung Cancer
Date of first enrollment	29/12/2025
Target sample size	15
Countries of recruitment	Australia,Japan,Canada,Japan,France,Japan,Greece,Japan,Hong Kong,Japan,Italy,Japan,Malaysia,Japan,Singapore,Japan,South Korea,Japan,Spain,Japan,Taiwan,Japan,Thailand,Japan,Turkey,Japan,United Kingdom,Japan,United States,Japan
Study type	Interventional
Intervention(s)	Investigational medical product: Drug: Firmonertinib 240 mg oral, daily firmonertinib tablet Other Names: AST2818 Drug: EGFR-TKI inhibitor based on investigator's choice osimertinib 80 mg oral, daily tablet OR afatinib 40 mg oral, daily tablet

Outcome(s)

Primary Outcome

-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. -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 Outcome

-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. -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. -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. -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. -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. -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. -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.

Key inclusion & exclusion criteria

Age minimum	>= 18age old
Age maximum	Not applicable
Gender	Both
Include 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.
Exclude criteria	1.Are unable or unwilling to swallow pills 2.Are unable to comply with study and follow-up procedures 3.Have NSCLC with any of the following EGFR mutations: exon 19 deletion, L858R, or C797S 4.Have had prior treatment with EGFR-targeted agents(eg, EGFR-TKIs, EGFR-targeted proteolysis-targeting chimeras [PROTACs], monoclonal antibodies, or bispecific antibodies) 5.Have had prior treatment with any systemic anti-cancer therapy for locally advanced or metastatic NSCLC not amenable to curative surgery or radiation, including chemotherapy, biologic therapy, immunotherapy, or any investigational drug 6.Have malabsorption syndrome or other conditions that would interfere with enteral absorption 7.Have pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures biweekly or more frequently Note: Indwelling pleural or abdominal catheters may be allowed, provided that the participant has adequately recovered from the procedure, is hemodynamically stable, and has symptomatically improved. 8.Have severe acute or chronic infections 9.Have had previous interstitial lung disease (ILD), including drug-induced ILD, or active ILD/active radiation pneumonitis 10.Have a history of or active clinically significant cardiovascular dysfunction 11.Have a mean resting corrected QT interval (QTc)> 470 ms, obtained from triplicate electrocardiograms (ECGs) with QT interval corrected by Fridericias method (QTcF) 12.Have clinically significant prolonged QT interval or other arrhythmia or clinical status that, in the opinion of investigators, may increase the risk of prolonged QT interval (eg, complete left bundle branch block, third-degree atrioventricular block, second-degree heart block, PR interval >250 ms, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first-degree relatives, serious hypokalemia, heart failure). For a list of drugs that may cause QT interval prolongation/torsades de pointes (TdP). 13.Have symptomatic hypercalcemia requiring the continued use of bisphosphonate therapy or denosumab 14.Have had a significant traumatic injury or major surgical procedure within 4 weeks prior to first dose of study treatment 15.Have chronic diarrhea; short bowel syndrome or significant upper GI surgery, including gastric resection; active inflammatory bowel disease (eg, Crohns disease or ulcerative colitis); or any active bowel inflammation (including diverticulitis) 16.Have any other diseases, pulmonary dysfunction, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, may affect the interpretation of the results, or renders participants at high risk from treatment complications (eg, uncontrolled hypertension, active bleeding) 17.Have had radiation therapy (other than palliative radiation for bone metastases as described below, or radiation for CNS metastases as described in inclusion criterion no. 14) as cancer therapy within 4 weeks prior to first dose of study treatment 18.Have had palliative radiation to bone metastases within 2 weeks prior to initiation of study drug 19.Have any unresolved toxicities from prior therapy (eg, adjuvant chemotherapy) of Grade >1 at initiation of study drug, with the exceptions of alopecia and prior chemotherapy-related Grade 2 neuropathy 20.Have a history of other malignancy within 3 years prior to screening, with the exception of participants with a negligible risk of metastases or death and/or treated with expected curative outcome (such as appropriately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, localized prostate cancer, or ductal carcinoma in situ) 21.Are pregnant or breastfeeding or are intending to become pregnant during the study or within 60 days after the final dose of study treatment 22.Have used a strong cytochrome P450 (CYP) 3A4 inhibitor within 7 days prior to the first dose of study treatment or a strong CYP3A4 inducer within 3 weeks prior to the first dose of study treatment 23.Have used traditional Chinese medicines/herbal medicines indicated for the treatment of cancer within 14 days prior to the first dose of study treatment 24.Have a history of allergic reactions to any components, including excipients, of the firmonertinib, osimertinib, and afatinib drug products