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A Study of IMC-RON8 in Advanced Solid Tumors

8 de octubre de 2018 actualizado por: Eli Lilly and Company

Phase 1 Study of the Anti-Ron Receptor Monoclonal Antibody IMC-RON8 in Patients With Advanced Solid Tumors Who No Longer Respond to Standard Therapy or for Whom No Standard Therapy is Available

A dose escalation study to determine the maximum tolerated dose of IMC-RON8 in participants with solid tumors. Participants can either be dosed once a week, or once every other week.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Tipo de estudio

Intervencionista

Inscripción (Actual)

39

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

  • Estados Unidos
    • Indiana
      • Indianapolis, Indiana, Estados Unidos, 46202
        • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician
    • Michigan
      • Detroit, Michigan, Estados Unidos, 48201
        • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician
    • New York
      • New York, New York, Estados Unidos, 10065
        • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician

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:

  • The participant has histologically-confirmed advanced primary or recurrent solid tumors that have not responded to standard therapy or for which no standard therapy is available
  • The participant has measurable or non-measurable disease
  • The participant has not received major surgery, prior chemotherapy, prior treatment with an investigational agent or device, or prior radiation therapy within 28 days prior to the first dose of study therapy
  • The participant has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0-2
  • The participant has adequate hematologic function
  • The participant has adequate renal function as defined by serum creatinine ≤1.5 times the institutional upper limit of normal (ULN)
  • The participant has a life expectancy >3 months

Exclusion Criteria:

  • The participant has received chemotherapy or therapeutic radiation therapy within 28 days prior to the first dose of study therapy
  • The participant has ongoing toxicities of >Grade 1 associated with any prior treatment
  • The participant has a known sensitivity to monoclonal antibodies or other therapeutic agents, or to agents of similar biologic composition as IMC-RON8
  • The participant has received treatment with any monoclonal antibodies within 6 weeks prior to first dose of study therapy
  • The participant has received treatment with agents specifically targeting the RON ligand or receptor within 6 weeks prior to first dose of study therapy
  • The participant has undergone a major surgical procedure, open biopsy, or experienced a significant traumatic injury within 28 days prior to the first dose of study therapy
  • The participant has an ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia (well controlled atrial fibrillation is permitted), psychiatric illness/social situations, active bleeding, or any other serious uncontrolled medical disorders in the opinion of the investigator
  • The participant has known or suspected brain or leptomeningeal metastases (participants with a history of brain metastases must have received definitive surgery or radiotherapy, be clinically stable, and may not be taking steroids; participants receiving anticonvulsants are eligible)
  • The participant has a serious or nonhealing active wound, ulcer, or bone fracture
  • The participant is currently using or has received a thrombolytic agent within 28 days prior to first dose of study therapy
  • The participant is receiving full-dose warfarin (participants receiving low-dose warfarin to maintain the patency of permanent, indwelling intravenous catheters are eligible if the international normalized ratio is <1.5)
  • The participant is receiving intravenous heparin

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
  • Modelo Intervencionista: Asignación Secuencial
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: IMC-RON8
A monoclonal antibody to human macrophage-stimulating 1-receptor-8 (RON8).
Biológico: IMC-RON8

5 milligrams per kilogram (mg/kg) intravenously (IV)

Once a week for each 4-week treatment cycle, for a total of four doses per cycle. The initial 4-week treatment cycle will be followed by a 2-week observation period.

Cohort 1

Otros nombres:
  • Narnatumab
  • LY3012219
Biológico: IMC-RON8

10 mg/kg IV

Once a week for each 4-week treatment cycle, for a total of four doses per cycle. The initial 4-week treatment cycle will be followed by a 2-week observation period.

Cohort 2

Otros nombres:
  • Narnatumab
  • LY3012219
Biológico: IMC-RON8

15 mg/kg IV

Once a week for each 4-week treatment cycle, for a total of four doses per cycle. The initial 4-week treatment cycle will be followed by a 2-week observation period.

Cohort 3

Otros nombres:
  • Narnatumab
  • LY3012219
Biológico: IMC-RON8

15 mg/kg IV

Once every 2 weeks for each 4-week treatment cycle, for a total of two doses per cycle.

Cohort 4

Otros nombres:
  • Narnatumab
  • LY3012219
Biológico: IMC-RON8

20 mg/kg IV

Once every 2 weeks for each 4-week treatment cycle, for a total of two doses per cycle.

Cohort 5

Otros nombres:
  • Narnatumab
  • LY3012219
Biológico: IMC-RON8

25 or 30 mg/kg IV

Once every 2 weeks for each 4-week treatment cycle, for a total of two doses per cycle.

Cohort 6

Otros nombres:
  • Narnatumab
  • LY3012219
Biológico: IMC-RON8

30, 35, or 40 mg/kg IV

Once every 2 weeks for each 4-week treatment cycle, for a total of two doses per cycle.

Cohort 7

Otros nombres:
  • Narnatumab
  • LY3012219
Biológico: IMC-RON8

20 or 25 mg/kg IV

Once every week for each 4-week treatment cycle, for a total of four doses per cycle.

Cohort 8

Otros nombres:
  • Narnatumab
  • LY3012219

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Maximum Tolerated Dose (MTD) of IMC-RON8
Periodo de tiempo: Baseline through end of study treatment (up to 48 weeks)
The MTD was the previous dose level to that in which 2 of 6 participants experienced dose-limiting toxicities (DLTs). DLTs were defined as any of the following events: Grade 4 neutropenia lasting >7 days; any Grade 3 or 4 neutropenia complicated by fever ≥38.5 degrees Celsius or infection, Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia complicated by hemorrhage; Grade 3 hepatic toxicity; or any Grade 3 or 4 nonhematologic toxicity (excluding alopecia, fatigue, anorexia, nausea, and vomiting that is controlled with antiemetics).
Baseline through end of study treatment (up to 48 weeks)

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Pharmacokinetics (PK): Maximum Concentration (Cmax) of IMC-RON8
Periodo de tiempo: First and fourth or fifth infusion: Predose, immediately postdose through 168 or 336 hours postdose
The Cmax of IMC-RON8 following the first and multiple IV infusions (the fourth infusion for the qw treatment regimen and the fifth infusion for the q2w treatment regimen) is reported. PK samples were collected per protocol and individual sampling times varied depending on the treatment arm and infusion (first or multiple). The geometric mean and geometric coefficient of variation (%CV) were calculated for treatment arms that had ≥3 participants who had evaluable PK samples for Cmax.
First and fourth or fifth infusion: Predose, immediately postdose through 168 or 336 hours postdose
PK: Area Under the Curve (AUC) of IMC-RON8
Periodo de tiempo: First and fourth or fifth infusion: Predose, immediately postdose through 168 or 336 hours postdose
The AUC from time 0 to the last quantifiable concentration [AUC(0-tlast)] of IMC-RON8 following the first IV infusion is reported along with the AUC for 1 dosing interval (AUC tau). Tau = fourth infusion through 168 hours post infusion for the qw regimen and the fifth infusion through 336 hours post infusion for the q2w regimen. PK samples were collected per protocol and individual sampling times varied depending on the treatment arm and infusion (first or multiple). The geometric mean and geometric coefficient of variation (%CV) were calculated for treatment arms that had ≥3 participants who had evaluable PK samples for AUC(0-tlast) or AUC tau.
First and fourth or fifth infusion: Predose, immediately postdose through 168 or 336 hours postdose
Immunogenicity of IMC-RON8
Periodo de tiempo: Prior to first infusion through study completion (up to 52 weeks)
An immunogenicity assay for IMC-RON8 was not developed due to the decision to not further develop IMC-RON8 based on preliminary results of this study.
Prior to first infusion through study completion (up to 52 weeks)
Pharmacodynamics: H-Score of Macrophage-Stimulating 1-Receptor-8 (RON8)
Periodo de tiempo: Prior to first infusion through 1 hour post last infusion (end of study treatment, up to 48 weeks)
The expression of RON8 was measured in cell membrane/cytoplasm by immunohistochemistry (IHC) methods that incorporated both intensity and distribution of staining. The H-Score was calculated by summing the percentage of cell staining at each intensity multiplied by the weighted intensity of staining: 0 (no staining), 1+ (weak staining), 2+ (medium staining), 3+ (strongest staining). H-Scores could range from a minimum score of 0 to a maximum score of 300; the maximum score indicated the strongest expression. Pharmacodynamic samples were collected per protocol and individual sampling times varied depending on the treatment group.
Prior to first infusion through 1 hour post last infusion (end of study treatment, up to 48 weeks)
Best Overall Tumor Response (Antitumor Activity of IMC-RON8 in the Treatment of Solid Tumors)
Periodo de tiempo: Baseline to measured PD (up to 48 weeks)
Response was defined using Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST, v 1.1) criteria. CR was the disappearance of all target and nontarget lesions; and any pathological lymph node (whether target or nontarget) must have had a reduction in short axis to <10 millimeters (mm) and normalization of tumor marker level of nontarget lesions. The disappearance of any intratumoral arterial enhancement in all target lesions was also required. PR was having at least a 30% decrease in sum of longest diameter of target lesions. PD was having at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase above nadir and the unequivocal progression of existing nontarget lesions. SD was small changes that did not meet the above criteria.
Baseline to measured PD (up to 48 weeks)

Otras medidas de resultado

Medida de resultado
Medida Descripción
Periodo de tiempo
Number of Participants Who Died
Periodo de tiempo: Baseline through study completion (up to 52 weeks)
The number of participants who died is reported by cause of death.
Baseline through study completion (up to 52 weeks)

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Eli Lilly and Company

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

1 de mayo de 2010

Finalización primaria (Actual)

1 de noviembre de 2013

Finalización del estudio (Actual)

1 de noviembre de 2013

Fechas de registro del estudio

Enviado por primera vez

6 de mayo de 2010

Primero enviado que cumplió con los criterios de control de calidad

6 de mayo de 2010

Publicado por primera vez (Estimar)

7 de mayo de 2010

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

15 de febrero de 2019

Última actualización enviada que cumplió con los criterios de control de calidad

8 de octubre de 2018

Última verificación

1 de octubre de 2018

Más información

Términos relacionados con este estudio

Palabras clave

Otros números de identificación del estudio

  • 13958
  • CP21-0901 (Otro identificador: ImClone Systems)
  • I5D-IE-JRCA (Otro identificador: Eli Lilly and Company)

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. .

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