HMPL-306 in Participants With Postoperative Residual or Recurrent Grade 2 Glioma Harboring IDH1 or IDH2 Mutations
A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase III Study to Evaluate the Efficacy and Safety of HMPL-306 in Participants With Postoperative Residual or Recurrent Grade 2 Glioma Harboring IDH1 or IDH2 Mutations
This study is a randomized, double-blind, placebo-controlled, multicenter Phase III clinical trial evaluating the efficacy and safety of HMPL-306 in participants with postoperative residual or recurrent grade 2 gliomas carrying IDH1 or IDH2 mutations.
Descripción general del estudio
Estado
Estado
Condiciones
Condiciones
Intervención / Tratamiento
Intervención / Tratamiento
Descripción detallada
This study plans to enroll approximately 210 participants with postoperative residual or recurrent grade 2 astrocytoma or oligodendroglioma carrying IDH1 or IDH2 mutations who have previously received only surgical treatment.
Participants meeting all enrollment eligibility criteria will be randomized in a 1:1 ratio to receive HMPL-306 250 mg or placebo matched to HMPL-306 administered orally once daily (QD). Participants will continue to receive study drug treatment in 28-day cycles until BIRC-confirmed PD, death, occurrence of intolerable toxicity, et al, whichever occurs first.
Participants in the placebo group with BIRC-confirmed PD, after evaluation, may cross over to the HMPL-306 group to receive HMPL-306 treatment.
Tipo de estudio
Tipo de estudio
Inscripción (Estimado)
Inscripción
Fase
Fase
- Fase 3
Contactos y Ubicaciones
Estudio Contacto
Estudio Contacto
- Nombre: Lu Chen
- Número de teléfono: 021 -2067 3000 - 5014
- Correo electrónico: Luc@hutch-med.com
Criterios de participación
Criterio de elegibilidad
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Have fully understood this study and voluntarily signed the ICF, willing to complete the planned visits, treatments, procedures, and laboratory tests during the study period;
- Age ≥18 years old;
- Patients with grade 2 oligodendroglioma or grade 2 astrocytoma;
- Have confirmed presence of IDH1 or IDH2 gene mutation, and obtained chromosome 1p/19q status;
- Have undergone at least 1 glioma surgery and have not received any other anti-glioma treatments, including chemotherapy and radiotherapy;
- Confirmed by BIRC, at least 1 measurable non-enhancing lesion meeting RANO 2.0 criteria using two-dimensional magnetic resonance imaging (MRI) measurement at screening;
- KPS ≥80;
- As judged by the investigator, life expectancy of ≥12 months;
- Adequate bone marrow, hepatic, renal, and coagulation function
Exclusion Criteria:
- Previously received any other anti-glioma treatment except for surgery, including chemotherapy, radiotherapy, targeted therapy, immunotherapy, or biological therapy, etc.;
- Participants assessed by the investigator as having high-risk factors, including but not limited to tumor involvement of the brainstem, or uncontrolled epilepsy;
- Participants with concurrent other malignant tumors or a history of other malignant tumors within 5 years prior to randomization (excluding cured basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, and ductal carcinoma in situ of the breast, etc.);
- Women who are pregnant (positive pregnancy test before medication) or breastfeeding;
- Known allergy to any component of HMPL-306;
- Administration of uridine diphosphate glucuronosyltransferase (UGT) 1A1 inhibitors or UGT1A3 inhibitors less than 1 week or 5 half-lives (whichever is longer) prior to randomization; administration of strong inducers of CYP3A less than 2 weeks or 5 half-lives (whichever is longer) prior to randomization;
- Presence of diseases or conditions that affect drug absorption;
- Participants will be excluded if there is any other disease, mental abnormality, metabolic abnormality, physical examination abnormality, or laboratory parameter abnormality of significant clinical significance, etc., which, in the investigator's judgment, may affect the participant's compliance, or place the participant at high risk, or affect the interpretation of study results, or if there is reason to suspect that the participant has a disease or condition unsuitable for the use of the study drug.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Cuadruplicar
Número de brazos
Armas e Intervenciones
Grupo de participantes/brazoGrupo de participantes/brazo |
Intervención / TratamientoIntervención / Tratamiento |
|---|---|
|
Experimental: HMPL-306 tablet
Participants in HMPL-306 group will receive HMPL-306 250 mg administered orally once daily (QD). Participants will continue to receive study drug treatment in 28-day cycles until BIRC-confirmed PD, death, occurrence of intolerable toxicity, et al, whichever occurs first. |
Participants meeting all enrollment eligibility criteria will be randomized in a 1:1 ratio to receive HMPL-306 or placebo matched to HMPL-306 administered orally once daily (QD). Participants in HMPL-306 group will receive HMPL-306 250 mg administered orally once daily (QD). Participants will continue to receive study drug treatment in 28-day cycles until BIRC-confirmed PD, death, occurrence of intolerable toxicity, et al, whichever occurs first. |
|
Comparador de placebos: Placebo
Participants in placebo group will receive placebo matched to HMPL-306 administered orally once daily (QD). Participants will continue to receive study drug treatment in 28-day cycles until BIRC-confirmed PD, death, occurrence of intolerable toxicity, et al, whichever occurs first. Participants in the placebo group with BIRC-confirmed PD, after evaluation, may cross over to the HMPL-306 group to receive HMPL-306 treatment. |
Participants meeting all enrollment eligibility criteria will be randomized in a 1:1 ratio to receive HMPL-306 or placebo matched to HMPL-306 administered orally once daily (QD). Participants in placebo group will receive placebo matched to HMPL-306 administered orally once daily (QD). Participants will continue to receive study drug treatment in 28-day cycles until BIRC-confirmed PD, death, occurrence of intolerable toxicity, et al, whichever occurs first. Participants in the placebo group with BIRC-confirmed PD, after evaluation, may cross over to the HMPL-306 group to receive HMPL-306 treatment. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
PFS assessed by BIRC (according to Response Assessment in Neuro-Oncology [RANO] 2.0 criteria)
Periodo de tiempo: Up to approximately 30 months
|
PFS(progression-free survival ):The time from the date of randomization to the date of first disease progression (PD) confirmed by BIRC(Blinded Independent Review Committee) or death from any cause |
Up to approximately 30 months
|
Medidas de resultado secundarias
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
TTNI
Periodo de tiempo: Up to approximately 36 months
|
TTNI(time to next intervention ):The time from the date of randomization to the date of first initiation of any subsequent anti-tumor therapy or all-cause death |
Up to approximately 36 months
|
|
TGR
Periodo de tiempo: every 6months,up to approximately 30 months
|
TGR( tumor growth rate) :The time from the date of randomization to the date of first disease progression (PD) confirmed by BIRC or death from any cause |
every 6months,up to approximately 30 months
|
|
TEAEs
Periodo de tiempo: Up to approximately 30 months
|
Treatment-emergent adverse events (TEAEs) are defined as all adverse medical events that occur after participants receive the investigational medicinal product, which may manifest as symptoms, signs, diseases, or laboratory abnormalities, but are not necessarily causally related to the investigational medicinal product. |
Up to approximately 30 months
|
|
PFS assessed by Investigator
Periodo de tiempo: Up to approximately 30 months
|
PFS ( progression-free survival) : the time from the date of randomization to the date of first PD confirmed by investigators or all-cause death |
Up to approximately 30 months
|
|
ORR
Periodo de tiempo: Up to approximately 30 months
|
ORR(objective response rate),defined as the proportion of participants with best overall response of complete response (CR), partial response (PR), and minor response (MR) |
Up to approximately 30 months
|
|
DCR
Periodo de tiempo: Up to approximately 30 months
|
DCR(disease control rate), defined as the proportion of participants with best overall response of CR(complete response), PR(partial response), MR(minor response), and SD(Stable Disease ) |
Up to approximately 30 months
|
|
TTR
Periodo de tiempo: Up to approximately 30 months
|
TTR(the time to response), defined as the time from the date of randomization to the date of first documented CR(complete response), PR(partial response), MR(minor response) |
Up to approximately 30 months
|
|
DoR
Periodo de tiempo: Up to approximately 30 months
|
DoR( duration of response), defined as the time from the date of first documented CR(complete response), PR(partial response), MR(minor response) to the date of first documented PD(Disease Progression) or death |
Up to approximately 30 months
|
|
(CR+PR) Rate
Periodo de tiempo: Up to approximately 30 months
|
CR+PR rate(the proportion of complete response and partial response), defined as the proportion of participants with best overall response of CR(complete response), and PR(partial response) |
Up to approximately 30 months
|
|
Time to CR+PR
Periodo de tiempo: Up to approximately 30 months
|
Time to CR+PR, defined as the time from the date of randomization to the date of first documented CR(complete response), or PR(partial response) |
Up to approximately 30 months
|
|
Duration of CR+PR
Periodo de tiempo: Up to approximately 30 months
|
Duration of CR+PR, defined as the time from the date of first documented CR or PR to the date of first documented PD or death from any cause, whichever occurs first |
Up to approximately 30 months
|
|
OS
Periodo de tiempo: Up to approximately 30 months
|
Overall survival (OS) :the time from the date of randomization to the date of all-cause death |
Up to approximately 30 months
|
|
HRQoL (health-related quality of life)assessed by the FACT-Br (Functional Assessment of Cancer Therapy-Brain)questionnaire
Periodo de tiempo: Up to approximately 30 months
|
The health-related quality of life (HRQoL) will be evaluated using the Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire in participants treated with HMPL-306 versus placebo |
Up to approximately 30 months
|
|
PK characteristics(plasma drug concentrations at each sampling time point)
Periodo de tiempo: Up to approximately 6 months
|
Plasma drug concentrations at each sampling time point |
Up to approximately 6 months
|
Colaboradores e Investigadores
Patrocinador
Patrocinador
Investigadores
Investigadores
- Investigador principal: Jinsong Wu, MD, Huashan Hospital
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Inicio del estudio
Finalización primaria (Estimado)
Finalización primaria
Finalización del estudio (Estimado)
Finalización del estudio
Fechas de registro del estudio
Enviado por primera vez
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Publicado por primera vez
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización publicada
Última actualización enviada que cumplió con los criterios de control de calidad
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Última verificación
Más información
Términos relacionados con este estudio
Otros números de identificación del estudio
Otros números de identificación del estudio
- 2026-306-00CH1
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.
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