Un ensayo para evaluar la seguridad y tolerabilidad de TST001 en tumores sólidos avanzados o metastásicos
Un ensayo clínico de fase I/IIa para evaluar la seguridad, la tolerabilidad y la farmacocinética de TST001 administrado como monoterapia o en combinación con nivolumab en pacientes con tumores sólidos metastásicos o localmente avanzados
This is an open label Phase I/IIa, First in Human trial of TST001, a recombinant humanized anti-Claudin 18.2 (CLDN18.2) IgG1 monoclonal antibody as monotherapy or in combination with nivolumab or standard of care. It is being tested against advanced and/or metastatic solid tumors including gastric, gastroesophageal junction, pancreatic cancers.
Descripción general del estudio
Estado
Intervención / Tratamiento
Descripción detallada
Part A of the trial will consist of two cohorts, one dosed every 2 weeks and one dosed every 3 weeks in a standard 3+3 design. Part A is the dose finding portion of the trial.
18 to 36 participants will be enrolled.
Part B consists of 3 cohorts:
Cohort A is for patients with previously untreated, unresectable, locally advanced or metastatic GC/GEJ adenocarcinoma. Patients will receive TST001 at 2mg/kg or 4mg/kg Q2W plus Nivolumab and mFOLFOX6. Alternative allocation of patients between the 2 doses will be performed. The first 6 patients at each dose level as the lead-in phase will not be selected on the basis of their tumor's CLDN18.2 expression. Approximately 12-42 patients will be enrolled in Cohort A.
Cohort B is for patients with GC/GEJ adenocarcinoma who have radiologically progressed following one or two prior systemic therapies. Patient will receive TST001 plus Nivolumab. No selection based on CLDN18.2 expression will be required for the safety run-in (3-6 patients). Patients with CLDN18.2 expression in tumor tissue tested by the central laboratory will be enrolled in the expansion phase. Safety run-in phase will follow 3+3 rule with two dose levels, TST001 3mg/kg and 6mg/kg Q3W combined with nivolumab. Approximately 30 patients will be enrolled in Cohort B including the patients in the safety run-in phase.
Cohort C is for patients with previously untreated, unresectable, locally advanced or metastatic histologically confirmed pancreatic adenocarcinoma; Patients will receive TST001 at 2mg/kg or 4mg/kg Q2W plus gemcitabine and albumin-bound paclitaxel. Alternative allocation of patients between the 2 doses will be performed. The first 6 patients at each dose level as the lead-in phase will not be selected on the basis of their tumor's CLDN18.2 expression. Approximately 12-42 patients will be enrolled in Cohort C.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 2
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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Arizona
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Gilbert, Arizona, Estados Unidos, 85234
- Banner MD Anderson
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Tucson, Arizona, Estados Unidos, 85724
- University of Arizona
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Connecticut
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New Haven, Connecticut, Estados Unidos, 06519
- Yale University
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Florida
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Sarasota, Florida, Estados Unidos, 34232
- Florida Cancer Specialists
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Georgia
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Atlanta, Georgia, Estados Unidos, 30033
- Emory University
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Kansas
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Kansas City, Kansas, Estados Unidos, 66160
- University of Kansas, School of Medicine
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Missouri
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St Louis, Missouri, Estados Unidos, 63110
- Washington University
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New York
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New York, New York, Estados Unidos, 10065
- Memorial Sloan Kettering
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Stony Brook, New York, Estados Unidos, 11794
- Stony Brook Cancer Center
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North Carolina
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Winston-Salem, North Carolina, Estados Unidos, 27157
- Wake Forest Baptist Comprehensive Cancer Center
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Ohio
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Canton, Ohio, Estados Unidos, 44718
- Gabrail Cancer Research
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Pennsylvania
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Gettysburg, Pennsylvania, Estados Unidos, 17325
- Pennsylvania Cancer Specialist Research Institute
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Pittsburgh, Pennsylvania, Estados Unidos, 15212
- Allegheny Hospital
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Tennessee
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Nashville, Tennessee, Estados Unidos, 37203
- Sarah Cannon Research Institute
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Nashville, Tennessee, Estados Unidos, 37232
- Vanderbilt University
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Texas
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Austin, Texas, Estados Unidos, 78704
- NEXT Oncology
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Washington
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Seattle, Washington, Estados Unidos, 98104
- Swedish Cancer Institute
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Wisconsin
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Milwaukee, Wisconsin, Estados Unidos, 53226
- Medical College of Wisconsin
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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:
- Male or female ≥ 18 years.
- Patients with histologically or cytologically confirmed, locally advanced or metastatic solid tumors.
Part A only:
* Patients must be: a) progressed after standard therapies, b) intolerant of standard therapies, or c) with a tumor type without standard therapy.
Part B only:
- Cohort A: Patients with previously untreated, unresectable, locally advanced or metastatic GC/GEJ adenocarcinoma; prior adjuvant or neoadjuvant therapy are allowed only if disease progressed or recurred at least 6 months after completion of these treatments. Patients may have received one infusion of mFOLFOX6 plus nivolumab during the screening period.
- Cohort B: Patients with GC/GEJ adenocarcinoma who have radiologically progressed following one or two prior systemic therapies; adjuvant or neoadjuvant therapy could be regarded as one line of therapy only if disease progressed or recurred during these treatments or within 6 months or less after completion of these treatments.
- Cohort C: Patients with previously untreated, unresectable, locally advanced or metastatic histologically confirmed pancreatic adenocarcinoma; prior adjuvant or neoadjuvant therapy are allowed only if disease progressed or recurred at least 6 months after completion of these treatments. Patients may have received up to 2 infusions of Gemcitabine + albumin-bound paclitaxel (with one week between each infusion) during the screening period.
- Eastern Cooperative Oncology Group Performance Status (ECOG PS): 0-1 .
- Patients with adequate cardiac, liver, renal function, etc.
Exclusion Criteria
- Symptomatic central nervous system metastases.
- Prior treatment with any CLDN18.2 target agents
- Allergy or sensitivity to TST001 or known allergies to comparable drugs
- Documented history of multiple other allergies requiring interventions
- Severe cardiovascular disease, including CVA, TIA, myocardial infarction, or unstable angina, NYHA class III or IV heart failure or uncontrolled arrhythmia within 6 months of study entry, severe QTc prolongation, concomitant risks for QTc prolongation.
- Concurrent malignancy within 5 years prior to entry except adequately treated certain types of cancer
- Active and clinically significant infections, known uncontrolled infections with hepatitis B, hepatitis C, known human immunodeficiency virus with acquired immunodeficiency syndrome related illness
- Any condition that the investigator or primary physician believes may not be appropriate for participating in the study.
Other protocol-defined Inclusion/Exclusion Criteria could apply.
.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: No aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: Part A Q2W
Dosed every 2 weeks IV with TST001, starting dose is 1 mg/kg, multiple dose levels will be tested. |
TST001 is a humanized IgG1 monoclonal antibody. |
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Experimental: Part A Q3W
Dosed every 3 weeks IV with TST001, starting dose is 3 mg/kg, and multiple dose levels will be tested. |
TST001 is a humanized IgG1 monoclonal antibody. |
|
Experimental: Part B Cohort A
Patients with previously untreated, unresectable, locally advanced or metastatic GC/GEJ adenocarcinoma. |
TST001 is a humanized IgG1 monoclonal antibody. Nivolumab is one of the PD-1 checkpoint inhibitors, and has proved clinical benefit for multiple late-stage malignancies mFOLFOX6 is a combination chemotherapy regimen including the drugs leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin. |
|
Experimental: Part B Cohort B
Patients with GC/GEJ adenocarcinoma who have radiologically progressed following one or two prior systemic therapies. |
TST001 is a humanized IgG1 monoclonal antibody. Nivolumab is one of the PD-1 checkpoint inhibitors, and has proved clinical benefit for multiple late-stage malignancies |
|
Experimental: Part B Cohort C
Patients with previously untreated, unresectable, locally advanced or metastatic histologically confirmed pancreatic adenocarcinoma. |
TST001 is a humanized IgG1 monoclonal antibody. Chemotherapy medication
Otros nombres:
Chemotherapy medication |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Participant Safety as characterized by frequency and severity of adverse events
Periodo de tiempo: up to 100 days following last dose
|
Characterization of TST001 safety profile including frequency and severity of adverse events that are related to treatment. |
up to 100 days following last dose
|
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Maximum Tolerated Dose (MTD or Recommended Phase 2 Dose (RP2D)
Periodo de tiempo: up to 100 days following last dose
|
As measured by number of participants experiencing dose related toxicity (DLT) in each escalating cohort |
up to 100 days following last dose
|
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Participant Safety and Tolerability of TST001 in combination with Nivolumab as characterized by frequency and severity of adverse events
Periodo de tiempo: Up to 100 days following last dose
|
Characterization of TST001 + Nivolumab safety profile including frequency and severity of adverse events that are related to treatment. |
Up to 100 days following last dose
|
|
Participant Safety and Tolerability of TST001 in combination with Nivolumab and mFOLFOX6 as characterized by frequency and severity of adverse events
Periodo de tiempo: Up to 100 days following last dose
|
Characterization of TST001 + Nivolumab + mFOLFOX6 safety profile including frequency and severity of adverse events that are related to treatment. |
Up to 100 days following last dose
|
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Participant Safety and Tolerability of TST001 in combination with gemcitabine and albumin-bound paclitaxel as characterized by frequency and severity of adverse events
Periodo de tiempo: Up to 100 days following last dose
|
Characterization of TST001 + Gemcitabine + albumin-bound paclitaxel safety profile including frequency and severity of adverse events that are related to treatment. |
Up to 100 days following last dose
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Immunogenicity
Periodo de tiempo: up to 30 days following last dose
|
by measurement of Incidence of anti-drug antibodies (ADA) |
up to 30 days following last dose
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Objective response rate (ORR)
Periodo de tiempo: up to 24 months, until disease progression or start of another anti-cancer therapy
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as measured by RECIST 1.1 |
up to 24 months, until disease progression or start of another anti-cancer therapy
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Duration of Response (DOR)
Periodo de tiempo: up to 24 months, until disease progression or start of another anti-cancer therapy
|
duration of response (DOR) |
up to 24 months, until disease progression or start of another anti-cancer therapy
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Progression free survival (PFS)
Periodo de tiempo: up to 24 months, until disease progression or start of another anti-cancer therapy
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as measured by RECIST v1.1 |
up to 24 months, until disease progression or start of another anti-cancer therapy
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PK parameters
Periodo de tiempo: Up to 30 days following last dose
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Maximum serum concentration (Cmax) |
Up to 30 days following last dose
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PK
Periodo de tiempo: Up to 30 days following last dose
|
time to reach maximum serum concentration (Tmax) |
Up to 30 days following last dose
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PK
Periodo de tiempo: Up to 30 days following last dose
|
Area Under the Curve |
Up to 30 days following last dose
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Director de estudio: Charlie Qi, MD, Suzhou Transcenta Therapeutics Co.
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
Términos MeSH relevantes adicionales
- Enfermedades del sistema endocrino
- Neoplasias por sitio
- Neoplasias
- Neoplasias Gastrointestinales
- Neoplasias del Sistema Digestivo
- Enfermedades del Sistema Digestivo
- Enfermedades Gastrointestinales
- Enfermedades del Estómago
- Neoplasias de glándulas endocrinas
- Enfermedades pancreáticas
- Neoplasias de Estómago
- Neoplasias pancreáticas
- Aminoácidos, péptidos y proteínas
- Proteínas
- Químicos orgánicos
- Compuestos heterocíclicos, 1 anillo
- Compuestos heterocíclicos
- Hidrocarburos
- Cicloparafinas
- Hidrocarburos, alicíclicos
- Hidrocarburos, cíclico
- Terpenos
- Anticuerpos, monoclonales, humanizados
- Anticuerpos, monoclonal
- Anticuerpos
- Inmunoglobulinas
- Inmunoproteínas
- Proteínas de la sangre
- Globulinas séricas
- Globulinas
- Taxaides
- Ciclodecanos
- Diterpenos
- Desoxicitidina
- Citidina
- Nucleósidos de pirimidina
- Pirimidinas
- Albúmina
- Paclitaxel
- Nivolumab
- Paclitaxel unido a albúmina
- Gemcitabina
Otros números de identificación del estudio
- TST001-1001
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
As described below. Patient personal data will be kept confidential as per HIPAA.
Marco de tiempo para compartir IPD
Clinical Study Report will become available approximately 60 to 90 days after last patient last visit. Each Investigator will receive one to keep. Protocol will be received prior to study start for each investigator.
Criterios de acceso compartido de IPD
Be an active investigator in the TST001-1001 trial
Tipo de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
- RSC
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.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .