A Study of the Safety, Pharmacokinetics, and Therapeutic Activity of RO6958688 in Combination With Atezolizumab in Participants With Locally Advanced and/or Metastatic Carcinoembryonic Antigen (CEA)-Positive Solid Tumors
10 de febrero de 2020 actualizado por: Hoffmann-La Roche
An Open-Label, Multicenter, Dose Escalation and Expansion Phase Ib Study to Evaluate the Safety, Pharmacokinetics, and Therapeutic Activity of RO6958688 in Combination With Atezolizumab in Patients With Locally Advanced and/or Metastatic CEA-Positive Solid Tumors
This is an open-label, multicenter, dose-escalation and expansion Phase Ib clinical study of RO6958688 in combination with atezolizumab.
Part I of the study is subdivided into parts IA and IB.
Part IA is dose escalation with a starting dose of 5 mg of RO6958688 given QW (once a week) and a fixed, flat dose of 1200 mg given Q3W (every 3 weeks) of atezolizumab, to evaluate the safety and determine the MTD of RO6958688 in combination with atezolizumab.
Part IB is a dose/schedule finding part that will explore different administration schedules of RO6958688 in combination with atezolizumab (1200 mg Q3W) to establish the appropriate dose/schedule of RO6958688 in combination with atezolizumab.
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Intervencionista
Inscripción (Actual)
228
Fase
- Fase 1
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
-
-
Ontario
-
Toronto, Ontario, Canadá, M5G 1Z5
- Princess Margaret Cancer Center
-
-
-
-
-
København Ø, Dinamarca, 2100
- Rigshospitalet; Onkologisk Klinik
-
-
-
-
-
Barcelona, España, 08003
- Hospital del Mar; Servicio de Oncologia
-
Barcelona, España, 08035
- Hospital Univ Vall d'Hebron; Servicio de Oncologia
-
Madrid, España, 28041
- Hospital Universitario 12 de Octubre; Servicio de Oncologia
-
Madrid, España, 28040
- Start Madrid-FJD, Hospital Fundacion Jimenez Diaz
-
Madrid, España, 28050
- START Madrid. Centro Integral Oncologico Clara Campal; CIOCC
-
-
Navarra
-
Pamplona, Navarra, España, 31008
- Clinica Universitaria de Navarra; Servicio de Oncologia
-
-
-
-
California
-
Santa Monica, California, Estados Unidos, 90404
- UCLA Cancer Center
-
Stanford, California, Estados Unidos, 94305
- Stanford Comprehensive Cancer Center
-
-
Colorado
-
Aurora, Colorado, Estados Unidos, 80045
- University of Colorado
-
-
Connecticut
-
New Haven, Connecticut, Estados Unidos, 06510
- Smilow Cancer Hospital at Yale- New Haven Oncology Investigational Drug Pharmacy
-
-
Massachusetts
-
Boston, Massachusetts, Estados Unidos, 02215
- Dana Farber Can Ins
-
-
New York
-
New York, New York, Estados Unidos, 10065
- Memorial Sloan Kettering Cancer Center
-
New York, New York, Estados Unidos, 10032
- Columbia Univ Med Ctr
-
-
North Carolina
-
Durham, North Carolina, Estados Unidos, 27710
- Duke Cancer Center
-
-
South Carolina
-
Charleston, South Carolina, Estados Unidos, 29425
- Medical University of South Carolina
-
-
Tennessee
-
Germantown, Tennessee, Estados Unidos, 38138
- Sarah Cannon Cancer Center
-
-
Texas
-
Houston, Texas, Estados Unidos, 77030
- MD Anderson Cancer Center
-
-
-
-
-
Lyon, Francia, 69373
- Centre Leon Berard; Departement Oncologie Medicale
-
Villejuif, Francia, 94805
- Institut Gustave Roussy
-
-
-
-
Campania
-
Napoli, Campania, Italia, 80131
- IRCCS IST. Tumori Fondaz. Pascale; S.C. Oncologia Medica,Melanoma,Immunoterapia E Terapie Innovative
-
-
Toscana
-
Siena, Toscana, Italia, 53100
- Azienda Ospedaliera Universitaria Senese, U.O.C. Immunoterapia Oncologica
-
-
-
-
-
Amsterdam, Países Bajos, 1066 CX
- Antoni Van Leeuwenhoek Ziekenhuis; Gastro-Enterologie
-
-
Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
Inclusion Criteria
- Confirmed locally advanced and/or metastatic solid tumor, with at least one tumor lesion of accessible non-critical location to biopsy, in participants who have progressed on a standard therapy, are intolerant to standard therapy, and/or are non-amenable to standard therapy
- Radiologically measurable and clinically evaluable disease (as per RECIST v1.1)
- Life expectancy (in the opinion of the investigator) of at least 12 weeks and lactate dehydrogenase (LDH) levels </= 2.5 ULN (upper limit of normal)
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1
- All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedure must have resolved to Grade </= 1 or returned to baseline except alopecia (any grade) and Grade 2 peripheral neuropathy
- Adequate hematological, liver, and renal function
- Negative serum pregnancy test within 7 days prior to study treatment in premenopausal women and women </= 2 years after start of menopause (menopause is defined as amenorrhea for more than 2 years)
- Participants must agree to remain abstinent or be willing to use effective methods of contraception as defined in the protocol
- Participants with non-colorectal cancer should have confirmed CEA expression in tumor tissue. For colorectal cancer (CRC), the CEA assessment should be performed but the result is not required for participant selection
Exclusion Criteria
- Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
- Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for at least 2 weeks prior to enrollment
- Leptomeningeal disease
- Participants with paraspinal, paratracheal, and mediastinal pathological lesions larger than 2 cm unless they are previously irradiated
- Malignancies within 5 years prior to enrollment, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome
- Significant, uncontrolled concomitant diseases which could affect compliance with the protocol or interpretation of results
- Uncontrolled hypertension, unstable angina, congestive heart failure (CHF), serious cardiac arrhythmia requiring treatment history of myocardial infarction within 6 months of enrollment
- Administration of a live, attenuated vaccine within 28 days before Cycle 1 Day 1 or anticipation that such a live attenuated vaccine will be required during the study
- Human Inmmunodeficiency Virus (HIV), active Hepatitis B or Hepatitis C (HCV)
- Severe infections within 28 days prior to Cycle 1 Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia or active tuberculosis
- Received oral or intravenous (IV) antibiotics within 14 days prior to Day 1
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
- Major surgery or significant traumatic injury less than 28 days prior to Cycle 1 Day 1 (excluding biopsies) or anticipation of the need for major surgery during study treatment
- Known history of autoimmune disease as defined in the protocol
- History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis (including drug induced) on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
- Participants with bilateral lung lesions and dyspnea and/or oxygen saturation level (SaO2) less than 92% (at rest, room air and exertion) or participants with lobectomy or pneumonectomy with lung metastases in the remaining lung and either dyspnea or SaO2 less than 92% (at rest, room air and exertion) at baseline
- Pregnant or breast-feeding
- Known hypersensitivity to any of the components of RO6958688 and atezolizumab; hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
- Investigational therapy (defined as treatment for which there is no regulatory authority approved indication) or last dose of prior immunotherapies within 28 days prior to Cycle 1 Day 1. Participants previously treated with anti-programmed death-ligand 1 (PD-L1), or anti-PD-1 are excluded
- Last dose of any approved anti-cancer therapy within 28 days prior to the first RO6958688 infusion
- Prior systemic corticosteroids greater than 10mg prednisone (or equivalent) within 14 days of Cycle 1 Day 1. Inhaled and/or topical steroids are permitted
- Expected need for regular immunosuppressive therapy
- Radiotherapy within the last 28 days before Cycle 1 Day 1 with the exception of limited-field palliative radiotherapy
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación Secuencial
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: Dose-Escalation (Part IA): RO6958688 + Atezolizumab
Participants will receive RO6958688 weekly (QW) at escalating doses starting at 5 mg, in combination with a fixed dose (1200 mg) of atezolizumab every 3 weeks (Q3W).
RO6958688 dosage will not exceed the MTD if defined in the BP29541 study.
|
Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg) by intravenous (IV) infusion.
Otros nombres:
RO6958688 is administered by IV infusion In Part IA: RO6958688 is administered weekly (QW) on days 1,8 and 15 of each 21-day cycle. In Part 1b: RO6958688 is administered weekly (QW) or every 3 weeks (Q3W). Cohort A: RO6958688 starting dose will be 100 mg either QW or Q3W. Step Up dose cohorts: RO6958688 starting dose will be 40mg and increase with each administration up to the MTD or 1200 mg whichever is lower. |
|
Experimental: Dose/Schedule Finding (Part IB): RO6958688 + Atezolizumab
Part IB will explore different RO6958688 administration schedules in combination with atezolizumab, consisting of: Cohort A: will compare the QW vs Q3W dosing schedules at a flat dose of RO6958688. Step Up dosing schedules: RO6958688 dose will start at 40 mg and increase with each administration up to the MTD or 1200 mg, whichever occurs first. |
Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg) by intravenous (IV) infusion.
Otros nombres:
RO6958688 is administered by IV infusion In Part IA: RO6958688 is administered weekly (QW) on days 1,8 and 15 of each 21-day cycle. In Part 1b: RO6958688 is administered weekly (QW) or every 3 weeks (Q3W). Cohort A: RO6958688 starting dose will be 100 mg either QW or Q3W. Step Up dose cohorts: RO6958688 starting dose will be 40mg and increase with each administration up to the MTD or 1200 mg whichever is lower. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
|---|---|
|
Porcentaje de participantes con toxicidades limitantes de dosis (DLT)
Periodo de tiempo: Día 1 hasta Día 21
|
Día 1 hasta Día 21
|
|
Number of Participants with Adverse Events (AEs)
Periodo de tiempo: Baseline up to 60 months
|
Baseline up to 60 months
|
|
Maximum-Tolerated Dose (MTD) of RO6958688
Periodo de tiempo: Part IA: Day 1 up to Day 21; Part IB Step-up Cohorts: Day 1 up to Day 7 after each dose escalation
|
Part IA: Day 1 up to Day 21; Part IB Step-up Cohorts: Day 1 up to Day 7 after each dose escalation
|
|
Recommended Phase II Dose (RP2D) of RO6958688
Periodo de tiempo: Day 1 up to 60 months
|
Day 1 up to 60 months
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Pharmacokinetic (PK): Area Under the Concentration-Time Curve (AUC) of RO6958688
Periodo de tiempo: Baseline up to 60 months
|
Baseline up to 60 months
|
|
|
PK: Volume of Distribution at Steady State (Vss) of RO6958688
Periodo de tiempo: Baseline up to 60 months
|
Baseline up to 60 months
|
|
|
PK: Maximum Serum Concentration (Cmax) of RO6958688
Periodo de tiempo: Baseline up to 60 months
|
Baseline up to 60 months
|
|
|
PK: Clearance (CL) of RO6958688
Periodo de tiempo: Baseline up to 60 months
|
Baseline up to 60 months
|
|
|
PK: AUC of Atezolizumab
Periodo de tiempo: Baseline up to 60 months
|
Baseline up to 60 months
|
|
|
PK: Vss of Atezolizumab
Periodo de tiempo: Baseline up to 60 months
|
Baseline up to 60 months
|
|
|
PK: Cmax of Atezolizumab
Periodo de tiempo: Baseline up to 60 months
|
Baseline up to 60 months
|
|
|
PK: CL of Atezolizumab
Periodo de tiempo: Baseline up to 60 months
|
Baseline up to 60 months
|
|
|
Pharmacodynamics: Immune Cell Numbers as Assessed using Flow Cytometry
Periodo de tiempo: Pre-infusion (1 hour before infusion start) on Day 1 of Cycles 1, 2, 3, 6; Cycle 1 Days 2 and 8 (cycle length=21 days)
|
Pre-infusion (1 hour before infusion start) on Day 1 of Cycles 1, 2, 3, 6; Cycle 1 Days 2 and 8 (cycle length=21 days)
|
|
|
Percentage of Participants with Objective Response (Partial Response [PR] or Complete Response [CR] as Assessed Using Response Evaluation Criteria in Solid Tumors [RECIST])
Periodo de tiempo: Baseline up to 60 months
|
Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
|
Baseline up to 60 months
|
|
Percentage of Participants with Disease Control (PR, CR, or Stable Disease [SD]) as Assessed Using RECIST
Periodo de tiempo: Baseline up to 60 months
|
Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
|
Baseline up to 60 months
|
|
Percentage of Participants with Stable Disease (SD) as Assessed Using RECIST
Periodo de tiempo: Baseline up to 60 months
|
Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
|
Baseline up to 60 months
|
|
Duration of Response (DOR) as Assessed Using RECIST
Periodo de tiempo: From initial objective response (PR or CR to the first disease progression or death from any cause (up to 60 months)
|
Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
|
From initial objective response (PR or CR to the first disease progression or death from any cause (up to 60 months)
|
|
Progression-Free Survival (PFS) according to RECIST V1.1
Periodo de tiempo: From first study treatment to the first occurrence of objective disease progression or death from any cause (up to 60 months)
|
Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
|
From first study treatment to the first occurrence of objective disease progression or death from any cause (up to 60 months)
|
|
Overall Survival (OS)
Periodo de tiempo: From first study treatment to death from any cause (up to 60 months)
|
Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
|
From first study treatment to death from any cause (up to 60 months)
|
|
Best Overall Response (BOR)
Periodo de tiempo: Baseline up to 60 months
|
Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
|
Baseline up to 60 months
|
Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
7 de enero de 2016
Finalización primaria (Actual)
13 de enero de 2020
Finalización del estudio (Actual)
13 de enero de 2020
Fechas de registro del estudio
Enviado por primera vez
6 de enero de 2016
Primero enviado que cumplió con los criterios de control de calidad
6 de enero de 2016
Publicado por primera vez (Estimar)
8 de enero de 2016
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
12 de febrero de 2020
Última actualización enviada que cumplió con los criterios de control de calidad
10 de febrero de 2020
Última verificación
1 de febrero de 2020
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- WP29945
- RG7802 (Otro identificador: Roche)
- 2015-003771-30 (Número EudraCT)
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. .