Un estudio para evaluar la eficacia y seguridad de WSD0922-FU en pacientes con cáncer de pulmón de células no pequeñas avanzado EGFRm +
Un estudio de fase I / II, multicéntrico, abierto y de un solo brazo para evaluar la seguridad, tolerabilidad, farmacocinética y eficacia de WSD0922-FU en el tratamiento del cáncer de pulmón de células no pequeñas avanzado
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 .
Descripción general del estudio
Estado
Intervención / Tratamiento
Descripción detallada
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.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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Anhui
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Hefei, Anhui, Porcelana, 230031
- Anhui Provincial Hospital
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Beijing Municipality
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Beijing, Beijing Municipality, Porcelana, 100021
- Cancer Hospital Chinese Academy of Medical Sciences
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Guangdong
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Guangzhou, Guangdong, Porcelana, 510062
- The First Affiliated Hospital, Sun Yat-sen University
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Henan
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Zhengzhou, Henan, Porcelana, 450000
- He'nan Cancer Hospital
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Shandong
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Jinan, Shandong, Porcelana, 250117
- Shandong Cancer Hospital
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Shanghai Municipality
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Shanghai, Shanghai Municipality, Porcelana, 200433
- Shanghai Pulmonary Hospital
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Shanghai, Shanghai Municipality, Porcelana, 200030
- Shanghai Chest Hospital
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Shanghai, Shanghai Municipality, Porcelana, 200123
- Shanghai East Hospital
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Sichuan
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Chengdu, Sichuan, Porcelana, 610041
- Sichuan Provincial Cancer Hospital
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Tianjin Municipality
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Tianjin, Tianjin Municipality, Porcelana, 300202
- Tianjin Medical University Cancer Institute and Hospital
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Zhejiang
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Hangzhou, Zhejiang, Porcelana, 310006
- The First Affiliated Hospital, Zhejiang University School of Medicine
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Taizhou, Zhejiang, Porcelana, 317000
- Taizhou Hospital of Zhejiang Province
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
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.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: No aleatorizado
- Modelo Intervencionista: Asignación Secuencial
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: Dose escalation (WSD0922-FU)
Patients receive WSD0922-FU PO QD on C0D1 to C0D3, then BID on C1D1 to C1D21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and blood sample collection on study. |
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
Otros nombres:
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Experimental: Dose expansion (WSD0922-FU)
Patients receive WSD0922-FU PO BID on C1D1 to C1D21 using dosage selected from Dose escalation. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and blood sample collection on study. |
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
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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ORR by IRC
Periodo de tiempo: every 6 weeks, up to 1 year
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proportion of patients with a best overall response of complete response or partial response |
every 6 weeks, up to 1 year
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PartA: To evaluate the safety of WSD0922-FU in patients with NSCLC
Periodo de tiempo: 8 months
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Safety (incidence and severity of adverse events [AE]) |
8 months
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PartA: To evaluate the tolerability of WSD0922-FU in patients with NSCLC
Periodo de tiempo: 8 months
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Incidence and quantity of dose-limiting toxicity (DLT) |
8 months
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|
PartA: To evaluate the Maximum Tolerated Dose (MTD) of WSD0922-FU in patients with NSCLC
Periodo de tiempo: 8 months
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Incidence of Dose-Limiting Toxicities (DLTs) |
8 months
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PartA: Recommended Phase II Dose (RP2D) of WSD0922-FU in patients with NSCLC
Periodo de tiempo: 8 months
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Recommended Phase II Dose (RP2D) |
8 months
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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To evaluate the safety of WSD0922-FU in patients with advanced non-small cell lung cancer
Periodo de tiempo: 12 months
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Treatment-Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events (TRAEs) |
12 months
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PK exposure parameter: Maximum Plasma Concentration (Cmax)
Periodo de tiempo: 12 months
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Maximum Plasma Concentration (Cmax) |
12 months
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PK exposure parameter: Time To Maximum Plasma Concentration (Tmax)
Periodo de tiempo: 12 months
|
Time To Maximum Plasma Concentration (Tmax) |
12 months
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PK exposure parameter: Area Under The Plasma Concentration-Time Curve From Time Zero To Time With Last Measurable Concentration (AUC0-t)
Periodo de tiempo: 12 months
|
Area Under The Plasma Concentration-Time Curve From Time Zero To Time With Last Measurable Concentration (AUC0-t) |
12 months
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PK exposure parameter: Area Under The Plasma Concentration-Time Curve From Time Zero To Infinity (AUC0-∞)
Periodo de tiempo: 12 months
|
Area Under The Plasma Concentration-Time Curve From Time Zero To Infinity (AUC0-∞) |
12 months
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PK exposure parameter: Terminal Elimination Half-Life (t½)
Periodo de tiempo: 12 months
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Terminal Elimination Half-Life (t½) |
12 months
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PK exposure parameter: Apparent Terminal Elimination Rate Constant (λz)
Periodo de tiempo: 12 months
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Apparent Terminal Elimination Rate Constant (λz) |
12 months
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PK exposure parameter: Apparent Clearance (CL)
Periodo de tiempo: 12 months
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Apparent Clearance (CL) |
12 months
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PK exposure parameter: Apparent volume of distribution (Vd)
Periodo de tiempo: 12 months
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Apparent volume of distribution (Vd) |
12 months
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PK exposure parameter: Mean Residence Time (MRT)
Periodo de tiempo: 12 months
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Mean Residence Time (MRT) |
12 months
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Steady state pharmacokinetic parameter: Area Under the Steady-State Concentration-Time Curve（AUCss）
Periodo de tiempo: 12 months
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Area Under the Steady-State Concentration-Time Curve（AUCss） |
12 months
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Steady state pharmacokinetic parameter: Area Under the Steady-State Concentration-Time Curve from 0 to Infinity（AUC0-∞,ss）
Periodo de tiempo: 12 months
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Area Under the Steady-State Concentration-Time Curve from 0 to Infinity（AUC0-∞,ss） |
12 months
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Steady state pharmacokinetic parameter: Area Under the Steady-State Concentration-Time Curve from 0 to Time t （AUC0-t,ss）
Periodo de tiempo: 12 months
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Area Under the Steady-State Concentration-Time Curve from 0 to Time t （AUC0-t,ss） |
12 months
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Steady state pharmacokinetic parameter: Average Steady-State Concentration（Cav）
Periodo de tiempo: 12 months
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Average Steady-State Concentration（Cav） |
12 months
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Steady state pharmacokinetic parameter: Steady-State Clearance（CLss）
Periodo de tiempo: 12 months
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Steady-State Clearance（CLss） |
12 months
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PK exposure parameter :Maximum Steady-State Concentration（Cmax,ss）
Periodo de tiempo: 12 months
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Maximum Steady-State Concentration（Cmax,ss） |
12 months
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PK exposure parameter : Minimum Steady-State Concentration（Cmin,ss）
Periodo de tiempo: 12 months
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Minimum Steady-State Concentration（Cmin,ss） |
12 months
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PK exposure parameter : Trough Concentration（Ctrough）
Periodo de tiempo: 12 months
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Trough Concentration（Ctrough） |
12 months
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PK exposure parameter : Fluctuation Degree（DF）
Periodo de tiempo: 12 months
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Fluctuation Degree（DF） |
12 months
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PK exposure parameter : Accumulation Ratio（Ra）
Periodo de tiempo: 12 months
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Accumulation Ratio（Ra） |
12 months
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PK exposure parameter : Time to Maximum Concentration at Steady State（Tmax,ss）
Periodo de tiempo: 12 months
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Time to Maximum Concentration at Steady State（Tmax,ss） |
12 months
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PK exposure parameter : Volume of Distribution Calculated from the Terminal Elimination Phase（Vz）
Periodo de tiempo: 12 months
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Volume of Distribution Calculated from the Terminal Elimination Phase（Vz） |
12 months
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ORR by investigators
Periodo de tiempo: every 6 week, up to 12 months
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proportion of patients with a best overall response of complete response or partial response |
every 6 week, up to 12 months
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|
Disease Control Rate (DCR)
Periodo de tiempo: every 6 weeks, up to12 months
|
the percentage of patients who have a best overall response of CR or PR or SD |
every 6 weeks, up to12 months
|
|
Duration of Response (DoR)
Periodo de tiempo: 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 |
every 6 weeks, up to 12 months
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PFS
Periodo de tiempo: every 6 weeks, up to 12 months
|
proportion of patients with the time from randomization until the date of objective disease progression or death |
every 6 weeks, up to 12 months
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OS
Periodo de tiempo: 24 months
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proportion of patients with the time from randomization until the date of objective disease progression or death |
24 months
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Caicun Zhou, MD, Shanghai East Hospital
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
producto fabricado y exportado desde los EE. UU.
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