This is a Multicenter, Open-label, Phase I/II Study to Explore the Safety, Tolerability, Pharmacokinetics (PK), and Preliminary Efficacy of GFH276 in Patients With Advanced NSCLC Harboring a RAS Mutation. (GFH276X1203)
A Phase Ib/II, Multicenter, Open-Label Study To Evaluate Safety, Efficacy And Pharmacokinetics Of GFH276 In Combination With Tislelizumab, Pemetrexed And Platinum (Carboplatin Or Cisplatin) As First-Line Therapy In Participants With Locally Advanced Or Metastatic Non-Squamous Non-Small-Cell Lung Cancer Harboring RAS Mutation
This is an open-label, multicenter Phase Ib/II clinical study evaluating GFH276 in combination with tislelizumab plus pemetrexed/platinum based regimen as first-line therapy in participants with locally advanced or metastatic non-squamous non-small-cell lung cancer (NSCLC) harboring RAS mutation or KRAS amplification.
Descripción general del estudio
Estado
Intervención / Tratamiento
Descripción detallada
This open-label, multicenter Phase Ib/II study enrolls participants with locally advanced or metastatic non-squamous NSCLC with RAS mutation or KRAS amplification, who have not received prior systemic anti-cancer therapy for advanced disease.
In Phase Ib, dose escalation of GFH276 will be performed in assigned arm to identify the recommended Phase 2 dose (RP2D) based on dose-limiting toxicity (DLT) and the overall safety profile. After RP2D determination, participants will be enrolled in Phase II to further evaluate the anti-tumor efficacy and long-term safety of each combination regimen. Study-related assessments will include tumor imaging, laboratory tests, adverse event monitoring, and pharmacokinetic sampling throughout the treatment period.
Participants will continue their assigned study treatment until confirmed disease progression, intolerable toxicity, withdrawal of consent, or study closure.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 2
- Fase 1
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Li Bai
- Número de teléfono: +86 2168821388
- Correo electrónico: lbai@genfleet.com
Copia de seguridad de contactos de estudio
- Nombre: Pingping Zhang
- Número de teléfono: +86 2168821388
- Correo electrónico: ppzhang@genfleet.com
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Histologically/cytologically confirmed locally advanced or metastatic non squamous NSCLC (AJCC 8th edition Stage IIIB-IV).
- Confirmed RAS mutation or KRAS amplification；tumor cell PD L1 test report available
- No prior systemic anti-tumor therapy for advanced disease
- At least 1 measurable lesion outside the central nervous system (CNS) per RECIST v1.1
- ECOG performance status 0 or 1
- Life expectancy>3 months
- Willing to provide written informed consent
- Fertile participants must use effective contraception
- Adequate organ function
Exclusion Criteria:
- Other active malignancy within 3 years
- Symptomatic brain metastases, leptomeningeal disease, spinal cord compression, or primary brain tumor
- History of active clinically significant cardiovascular dysfunction
- Known to harbor other targetable driver gene alterations
- Presence of active infection (HIV, HBV, HCV,)
- Prior anti-tumor therapy within 28 days or 5 half-lives
- Diagnosis of unstable thrombotic events requiring therapeutic intervention within 3 months prior to the first dose of study treatment.
- Hypersensitivity to study drugs, or inability to swallow tablets or comply with study procedures.
- History of central nervous system (CNS)disease
- Presence of clinically significant interstitial lung disease, radiation pneumonitis, or immune-related pneumonia that requires treatment.
- With uncontrollable or symptomatic pleural effusion, ascites, or pericardial effusion.
- Active autoimmune disease requiring systemic treatment.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: GFH276 ±Tislelizumab + AP
GFH276 once daily; Tislelizumab 200 mg, IV; AP: Pemetrexed 500 mg/m², IV; Cisplatin/Carboplatin 75 mg/m²/AUC=5, IV, every 3 weeks |
Oral GFH276, administered at specified dose on schedule. Tislelizumab 200 mg, intravenous infusion, once every 3 weeks.or without Tislelizumab Pemetrexed 500 mg/m², intravenous infusion, once every 3 weeks. Cisplatin 75 mg/m², intravenous infusion, once every 3 weeks. Carboplatin at AUC=5, intravenous infusion, once every 3 weeks. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Phase Ib:Incidence of Dose-Limiting Toxicity (DLT) Events
Periodo de tiempo: First 21 days
|
The incidence of DLT events |
First 21 days
|
|
Phase II:Objective Response Rate (ORR)
Periodo de tiempo: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
|
Assessed by investigators according to RECIST 1.1 |
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
|
|
Phase Ib:Incidence and Severity of Adverse Events (AE) and Serious Adverse Events (SAE)
Periodo de tiempo: From the first dose until 30 days after the last dose, assessed up to 36 months
|
The incidence and severity of AEs and SAEs，according to NCI CTCAE，v6.0 |
From the first dose until 30 days after the last dose, assessed up to 36 months
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
DCR
Periodo de tiempo: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
|
Disease Control Rate (DCR) |
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
|
|
DoR
Periodo de tiempo: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
|
Duration of Response assessed by investigators |
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
|
|
TTR
Periodo de tiempo: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
|
Time To Response assessed by investigators |
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
|
|
PFS
Periodo de tiempo: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
|
Progression-Free Survival (PFS) per Response Evaluation Criteria according to RECIST 1.1, as Determined by investigators |
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
|
|
OS
Periodo de tiempo: From the first dose until date of death from any cause, assessed up to 36 months
|
Overall Survival |
From the first dose until date of death from any cause, assessed up to 36 months
|
|
Phase II: Incidence and Severity of AE and SAE
Periodo de tiempo: From the first dose until 30 days after the last dose, assessed up to 36 months
|
Incidence and Severity of AE and SAE，Assessed according to CTCAE 6.0 |
From the first dose until 30 days after the last dose, assessed up to 36 months
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Ziming Li, MD, Shanghai Chest Hospital
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
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
Palabras clave
Términos MeSH relevantes adicionales
- Neoplasias por sitio
- Neoplasias
- Enfermedades de las vías respiratorias
- Enfermedades pulmonares
- Neoplasias de las vías respiratorias
- Neoplasias torácicas
- Neoplasias Pulmonares
- Carcinoma Broncogénico
- Neoplasias Bronquiales
- Carcinoma de pulmón de células no pequeñas
- Aminoácidos, péptidos y proteínas
- Químicos orgánicos
- Compuestos heterocíclicos
- Compuestos heterocíclicos, 2 anillos
- Compuestos heterocíclicos, anillo fusionado
- Químicos inorgánicos
- Compuestos de cloro
- Compuestos de nitrógeno
- Complejos de coordinación
- Guanina
- Hipoxantino
- Purinones
- Purinas
- Glutamatos
- Aminoácidos, ácido
- Aminoácidos
- Aminoácidos, dicarboxílico
- Compuestos de platino
- Pemetrexed
- Carboplatino
- Cisplatino
- tislelizumab
Otros números de identificación del estudio
- GFH276X1203
Plan de datos de participantes individuales (IPD)
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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.
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