EGFR Mutation Positive Advanced Non-Small Cell Lung Cancer
Conditions
Keywords
NSCLC, EGFR, C797S, BM
Brief summary
This study is a multicenter, open label, single-arm phase I/II clinical trial of WSD0922-FU for patients with locally advanced or metastatic non-small cell lung cancer whose disease has progressed with thrid-generation EGFR-TKI .
Detailed description
WSD0922-FU is a potent reversible inhibitor of both the single EGFRm+ and dual EGFRm+/C797S+ receptor forms of EGFR with selectivity margin over wild-type EGFR. This study aims to explore the safety, tolerability, pharmacokinetic characteristics and efficacy of WSD0922-FU in patients with non-small cell lung cancer (NSCLC) with C797S mutation after first-line third-generation EGFR-TKI resistance.
Interventions
DRUGWSD0922-FU
Procedure: Biospecimen Collection - blood samples Undergo collection of blood samples Procedure: Computed Tomography and/or Magnetic Resonance Imaging Undergo CT and/or MRI Drug: WSD0922-FU Given PO
Sponsors
Wayshine Biopharm, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Part A (Dose escalation and expansion study) ; Part B (single-arm extension study).
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-75 years old (including the threshold value), gender is not limited; * Locally advanced or metastatic NSCLC confirmed by pathology; * Patients who have been genetically tested to carry EGFR sensitive mutations; * Blood samples must be provided for testing and must be taken during or after disease progression following the last EGFR TKI inhibitor treatment; * Must have a minimum life expectancy of \>= 3 months; * At least one measurable tumor lesion according to RECIST version 1.1; Previous radiotherapy-treated lesions cannot be used as target lesions unless imaging studies show clear progression of the lesions. * Physical Status (ECOG PS) score was 0-1; * Have full organ function; * Eligible patients (male and female) who are fertile must agree to use a reliable contraceptive method ; * Subjects are required to give informed consent to this study before the experiment and sign a written informed consent voluntarily.
Exclusion criteria
* Received chemotherapy, radiotherapy, biological therapy, targeted therapy, endocrine therapy, immunotherapy, or other anti-tumor drug treatments within 4 weeks before the first administration of the study drug. * Have previously received more than one EGFR-TKI inhibitor; * Received other unlisted clinical study drugs or treatments within 4 weeks before the first administration. * Received major organ surgery (excluding puncture biopsy) or significant trauma within 4 weeks before the first administration, or require elective surgery during the trial period. * Used strong CYP3A4 inhibitors or strong CYP3A4 inducers within 7 days before the first use of the study drug. * Known active brain metastasis or progression evidence. * Other primary malignant tumors within 2 years before the first administration of the study drug. * Adverse reactions from previous anti-tumor treatments have not recovered to NCI-CTCAE v5.0 grade ≤1 (except for toxicities judged by the researcher to have no safety risks, such as hair loss, grade 2 peripheral neurotoxicity, and stable thyroid function after hormone replacement therapy). * Skin/pressure ulcers, chronic leg ulcers, known active gastric ulcers, or non-healing wounds. * History of severe allergies, or allergies to any active or inactive ingredients of the study drug; * Severe infections requiring intravenous antibiotic infusion or hospitalization at the time of screening; or uncontrollable active infections within 4 weeks before administration; * Known active or suspected autoimmune diseases; or known active ocular diseases (such as active wet age-related macular degeneration, diabetic retinopathy with macular edema); * Human immunodeficiency virus (HIV) (HIV1/2 antibody) positive, syphilis spirochete antibody positive . * Patients with interstitial lung disease. * History of severe cardiovascular diseases. * Unable to orally swallow medication, or there is a condition that significantly affects gastrointestinal absorption as judged by the researcher; * Clinical intervention is required for pleural effusion, ascites (excluding subjects who do not need drainage and have been stable for more than 2 weeks after drainage). * Known alcohol or drug dependence. * Mental disorders or poor compliance; * Pregnant or lactating women; * The investigator believes that the subject has other reasons that make them unsuitable for participating in this clinical study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR by IRC | every 6 weeks, up to 1 year | proportion of patients with a best overall response of complete response or partial response |
| PartA: To evaluate the safety of WSD0922-FU in patients with NSCLC | 8 months | Safety (incidence and severity of adverse events \[AE\]) |
| PartA: To evaluate the tolerability of WSD0922-FU in patients with NSCLC | 8 months | Incidence and quantity of dose-limiting toxicity (DLT) |
| PartA: To evaluate the Maximum Tolerated Dose (MTD) of WSD0922-FU in patients with NSCLC | 8 months | Incidence of Dose-Limiting Toxicities (DLTs) |
| PartA: Recommended Phase II Dose (RP2D) of WSD0922-FU in patients with NSCLC | 8 months | Recommended Phase II Dose (RP2D) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK exposure parameter: Area Under The Plasma Concentration-Time Curve From Time Zero To Infinity (AUC0-∞) | 12 months | Area Under The Plasma Concentration-Time Curve From Time Zero To Infinity (AUC0-∞) |
| PK exposure parameter: Terminal Elimination Half-Life (t½) | 12 months | Terminal Elimination Half-Life (t½) |
| PK exposure parameter: Apparent Terminal Elimination Rate Constant (λz) | 12 months | Apparent Terminal Elimination Rate Constant (λz) |
| PK exposure parameter: Apparent Clearance (CL) | 12 months | Apparent Clearance (CL) |
| PK exposure parameter: Apparent volume of distribution (Vd) | 12 months | Apparent volume of distribution (Vd) |
| PK exposure parameter: Mean Residence Time (MRT) | 12 months | Mean Residence Time (MRT) |
| Steady state pharmacokinetic parameter: Area Under the Steady-State Concentration-Time Curve（AUCss） | 12 months | Area Under the Steady-State Concentration-Time Curve（AUCss） |
| Steady state pharmacokinetic parameter: Area Under the Steady-State Concentration-Time Curve from 0 to Infinity（AUC0-∞,ss） | 12 months | Area Under the Steady-State Concentration-Time Curve from 0 to Infinity（AUC0-∞,ss） |
| Steady state pharmacokinetic parameter: Area Under the Steady-State Concentration-Time Curve from 0 to Time t （AUC0-t,ss） | 12 months | Area Under the Steady-State Concentration-Time Curve from 0 to Time t （AUC0-t,ss） |
| Steady state pharmacokinetic parameter: Average Steady-State Concentration（Cav） | 12 months | Average Steady-State Concentration（Cav） |
| Steady state pharmacokinetic parameter: Steady-State Clearance（CLss） | 12 months | Steady-State Clearance（CLss） |
| PK exposure parameter : Fluctuation Degree（DF） | 12 months | Fluctuation Degree（DF） |
| PK exposure parameter : Minimum Steady-State Concentration（Cmin,ss） | 12 months | Minimum Steady-State Concentration（Cmin,ss） |
| PK exposure parameter : Trough Concentration（Ctrough） | 12 months | Trough Concentration（Ctrough） |
| PK exposure parameter : Time to Maximum Concentration at Steady State（Tmax,ss） | 12 months | Time to Maximum Concentration at Steady State（Tmax,ss） |
| PK exposure parameter : Volume of Distribution Calculated from the Terminal Elimination Phase（Vz） | 12 months | Volume of Distribution Calculated from the Terminal Elimination Phase（Vz） |
| To evaluate the safety of WSD0922-FU in patients with advanced non-small cell lung cancer | 12 months | Treatment-Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events (TRAEs) |
| ORR by investigators | every 6 week, up to 12 months | proportion of patients with a best overall response of complete response or partial response |
| Disease Control Rate (DCR) | every 6 weeks, up to12 months | the percentage of patients who have a best overall response of CR or PR or SD |
| Duration of Response (DoR) | every 6 weeks, up to 12 months | proportion of patients with the time from the date of first documented response until the date of documented progression or death in the absence of disease progression |
| PFS | every 6 weeks, up to 12 months | proportion of patients with the time from randomization until the date of objective disease progression or death |
| OS | 24 months | proportion of patients with the time from randomization until the date of objective disease progression or death |
| PK exposure parameter :Maximum Steady-State Concentration（Cmax,ss） | 12 months | Maximum Steady-State Concentration（Cmax,ss） |
| PK exposure parameter : Accumulation Ratio（Ra） | 12 months | Accumulation Ratio（Ra） |
| PK exposure parameter: Maximum Plasma Concentration (Cmax) | 12 months | Maximum Plasma Concentration (Cmax) |
| PK exposure parameter: Time To Maximum Plasma Concentration (Tmax) | 12 months | Time To Maximum Plasma Concentration (Tmax) |
| PK exposure parameter: Area Under The Plasma Concentration-Time Curve From Time Zero To Time With Last Measurable Concentration (AUC0-t) | 12 months | Area Under The Plasma Concentration-Time Curve From Time Zero To Time With Last Measurable Concentration (AUC0-t) |
Countries
China
Contacts
Primary Contactlily liu, MD
Backup ContactWei Zhong, PhD
Outcome results
None listed