Non Small Cell Lung Cancer
Conditions
Keywords
FHND9041, phase Ⅲ
Brief summary
The goal of this clinical trial is to evaluate the effectiveness and safety of FHND9041 compared to afatinib as first-line treatments for epidermal growth factor receptor mutation-positive (EGFRm+) locally advanced or metastatic non-small cell lung cancer (NSCLC). The main questions it aims to answer are: * Does FHND9041 improve progression-free survival (PFS) compared to afatinib? * Are there differences in safety profiles between FHND9041 and afatinib? Researchers will compare FHND9041 (80 mg, orally, once daily) with afatinib (40 mg, orally, once daily) in a randomized, open-label, parallel-controlled, multicenter Phase III trial. Participants who meet the inclusion criteria, including having EGFR mutations (L858R and/or Exon 19 deletion) and no prior treatment, will be randomly assigned in a 1:1 ratio to either the FHND9041 group or the afatinib group. Treatment will continue until disease progression, intolerable drug-related toxicity, or other pre-specified treatment discontinuation criteria are met. Study Procedures: Participants will: * Be screened for eligibility and randomly assigned to one of two groups. * Receive study drugs per their assigned group. * Undergo regular tumor assessments by Response Evaluation Criteria in Solid Tumors, version 1.1( RECIST 1.1) every six weeks during the first 18 cycles, then every nine weeks until disease progression. For intracranial efficacy, Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM ) criteria will be applied. * Participate in pharmacokinetic studies (FHND9041 group only) with blood samples collected pre-dose at specified cycles and on the day of discontinuation. After disease progression, participants will be followed for survival every three months.
Interventions
DRUGFHND9041
FHND9041 is a novel therapeutic agent targeting EGFR mutations. Participants will take an 80 mg oral dose once daily until disease progression, intolerable toxicity, or meeting other study-defined discontinuation criteria.
DRUGAfatinib
Afatinib is an approved, second-generation, irreversible EGFR tyrosine kinase inhibitor used as a standard first-line treatment for non-small cell lung cancer (NSCLC) with EGFR-sensitive mutations, such as L858R and Exon 19 deletions. Participants in this arm will take a 40 mg oral dose once daily. Afatinib serves as the active comparator in this study to evaluate the efficacy and safety of FHND9041.
Sponsors
Jiangsu Chia Tai Fenghai Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Months to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants aged ≥ 18 years, with no gender restrictions. * Histologically or cytologically confirmed diagnosis of locally advanced or metastatic non-small cell lung cancer (NSCLC), including patients with recurrent disease following prior surgical treatment or newly diagnosed Stage IIIb, IIIc, or IV NSCLC (staging based on the 8th edition of the AJCC guidelines). * No prior systemic anti-tumor therapy (e.g., standard chemotherapy, targeted therapy, biological therapy, or immunotherapy). Patients who have received adjuvant or neoadjuvant therapy (chemotherapy, radiotherapy, or other treatments) are eligible if disease progression occurred at least 6 months after completing the prior treatment. * Presence of a confirmed EGFR-positive gene mutation sensitive to EGFR-TKI treatment, including exon 19 deletion or L858R mutation. * At least one measurable tumor lesion at baseline that meets the following criteria: No prior radiotherapy or biopsy during the screening period (if the subject has only one measurable lesion, fine-needle aspiration cytology to confirm genetic status is permitted; however, baseline imaging must be performed at least 7 days after the biopsy). Lesion can be accurately measured with a longest diameter ≥ 10 mm (or a short axis ≥ 15 mm for lymph nodes). Lesion can be assessed using CT or MRI, with the same imaging modality used consistently for subsequent evaluations. * An Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1. * A life expectancy of ≥ 3 months. * Female participants of childbearing potential must have a negative serum pregnancy test prior to enrollment. Male and female participants with reproductive potential must agree to maintain abstinence or use effective contraception during the study and for at least 3 months following the last dose of the investigational drug. * Participants must demonstrate the ability to understand the study objectives and procedures, comply with protocol requirements, cooperate with study-related visits, and provide written informed consent, indicating their voluntary participation.
Exclusion criteria
● Pre-treatment History: Major Surgery: Subjects who have undergone major surgery within 28 days before the first dose of the study drug. For the purposes of this study, major surgery refers to level 3 and level 4 surgeries as defined in the Administrative Measures for the Clinical Application of Medical Technology (implemented on May 1, 2009). Radiotherapy: Subjects who have received local radiotherapy or palliative radiotherapy for bone metastasis within 14 days prior to the first dose of the study drug. CYP3A4 Interactions: Subjects who have received a strong CYP3A4 inhibitor or a strong inducer within 7 days before the first dose, or who need to continue using these drugs during the study period. Chinese Herbal Medicines: Subjects who have received Chinese herbal medicines or proprietary Chinese medicine preparations for anti-tumor indications within 7 days prior to the first dose, or who need to continue using these during the study period. QT Prolongation Medications: Subjects who are receiving drug treatments known to prolong the QTc interval or potentially cause torsades de pointes, and who need to continue using these medications during the study period. * Unhealed Toxicity: Subjects who have unresolved toxic reactions of grade ≥ 2 (according to NCI-CTCAE 5.0 standards) related to previous treatments, except for hair loss and grade 2 neuropathy caused by platinum-based drugs. * Spinal Cord Compression/Brain Metastases: Subjects with spinal cord compression or brain metastases, except those who are asymptomatic, stable, and have not required steroid treatment for at least 4 weeks prior to the start of the study. Subjects with brain metastases who have received local radiotherapy must show stable symptoms for at least 28 days following completion of the radiotherapy. * Uncontrolled Systemic Diseases: Subjects with severe or uncontrolled systemic diseases (e.g., hypertension not controlled by medication, active bleeding disorders) that, in the investigator's opinion, may interfere with the participant's ability to comply with the study protocol. * Active Infections: Subjects with active infections that require medical treatment, including HBV (HBsAg positive, HBV-DNA \> 1000 cps/ml or 200 IU/ml, and AST or ALT \> 2.0 ULN), HCV (HCV antibody positive and HCV-RNA ≥ 1000 IU/mL), HIV, syphilis, or other serious infections. ● Gastrointestinal Dysfunction: Subjects with clinically significant gastrointestinal issues that may affect the intake, transport, or absorption of the study drug. This includes inability to take oral medication, uncontrolled nausea or vomiting, history of extensive gastrointestinal resection, unresolved recurrent diarrhea, or gastrointestinal diseases such as Crohn's disease or ulcerative colitis requiring long-term use of proton pump inhibitors (PPI). ● Cardiac
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | 24 months | The time from randomization to the first documented disease progression ( assessed by investigators) or death due to any cause, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 36 months | The time from randomization to death due to any cause. |
| Duration of Response (DoR) | 24 months | The time from the first documented CR or PR to the first documented disease progression or death, whichever occurs first. |
| Disease Control Rate (DCR) | 24 months | The proportion of participants with confirmed CR, PR, or stable disease (SD) for at least 6 weeks |
| Objective Response Rate (ORR) | 24 months | The proportion of participants with confirmed complete response (CR) or partial response (PR) |
| European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 ( EQRTC-C30) | 24 months | Change from baseline in quality of life (QoL) scores using the EQRTC-C30 questionnaire. The scale ranges from 0 to 100, where higher scores indicate better quality of life. |
| European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer Module 13(LC13) | 36 months | Change from baseline in quality of life (QoL) scores using the LC13 questionnaire. The scale ranges from 0 to 100, where higher scores indicate better quality of life. |
| Lung Cancer Symptom Scale(LCSS) | 36 months | Change from baseline in quality of life (QoL) scores using the LCSS questionnaire. The scale ranges from 0 to 100, where higher scores indicate better quality of life. |
| Depth of Response (DepOR) | 24 months | The maximum percentage change in the sum of target lesion diameters from baseline |
Countries
China
Outcome results
None listed