E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic or Advanced Non-Small Cell Lung Cancer (NSCLC) |
Cáncer de pulmón no microcítico (CPNM) metastásico o avanzado. |
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E.1.1.1 | Medical condition in easily understood language |
Lung Cancer |
Cáncer de Pulmón |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the Phase 1 study is to establish the Recommended Phase 2 Dose (RPTD) of veliparib in combination with nivolumab and platinum doublet chemotherapy in subjects with metastatic or advanced NSCLC.
The primary objective of the Phase 2 study is to assess whether the addition of nivolumab to veliparib in combination with platinum doublet chemotherapy results in improved progression free survival (PFS) compared to veliparib with platinum doublet chemotherapy alone. |
El objetivo primario del studio de fase 1 es establecer la dosis máxima recomendada para fase 2 (DMT) de veliparib en combinación con nivolumab y quimioterapia basada en doblete de platino en sujetos con CPNM metastásico o avanzado. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives of the dose escalation study are to assess the safety and pharmacokinetics of this drug combination and to obtain a preliminary evaluation of antitumor activity using RECIST (version 1.1).
Secondary objectives of the Phase 2 study are to compare overall survival (OS), objective response rate (ORR) and duration of response (DOR) between the two treatment arms. |
Los objetivos secundarios del studio de escalado de dosis son determiner la seguridad y la farmacocinética de esta combinación de medicamento y así obtener una evaluación preliminary de la actividad antitumoral según RECIST (version 1.1). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Participant must have life expectancy greater than 12 weeks. - Participant must have cytologically or histologically confirmed Non-small Cell Lung Cancer (NSCLC). - Participant must have metastatic or advanced NSCLC (Stage IIIB or IV) that is not amenable to surgical resection or radiation or chemoradiation with curative intent at time of study screening. - Participant must have at least 1 unidimensional measurable NSCLC lesion on a computed tomography (CT) scan as defined by Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1). - Participant must have resolution to grade 1 or lower of any toxic effects (excepting alopecia) of the most recent therapy prior to Cycle 1 Day 2. - Participant must have an Eastern Cooperative Oncology Group (ECOG) Performance score of 0 to 1. - Participant must have adequate bone marrow, renal, and hepatic function. |
- El participante debe tener una expectativa de vida mayor a 12 semanas - El participante debe tener un cancer de pulmón no microcítico (CPNM) confirmado citológico o histológicamente. - El participante debe tener CPNM metastásico o avanzado (grado IIIB IV) no sujeto a resección quirúrgica o radioterapia o quimioradioterapia con intención curativa en el momento de la selección. - El participante debe tener al menos una lesión de CPNM no medible en una sola dimension por tomografía axial computerizada (TAC) definido por los “Criterios de Evaluación de Respuesta en Tumores Sólidos” (RECIST). - El participante debe tener una resolución a grado 1 o más bajo de cualquier reacción tóxica (excepto alopecia) de la terapia más reciente anterior al Ciclo 1 Día 2. - El participante debe tener una puntuación del estado general basado en el “Grupo de Oncología Cooperativo del Este” (ECOG) de 0 a 1. - El participante debe tener adecuadas funciones hepáticas, renales y de médula ósea. |
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E.4 | Principal exclusion criteria |
- Participant has received prior cytotoxic chemotherapy (including chemotherapy in combination with radiotherapy) for NSCLC, except for adjuvant or neoadjuvant therapy accompanied by surgery with curative intent that was completed one year prior to Cycle 1 Day-2. - Participant has received prior therapy with a Poly-(ADP-ribose)-Polymerase (PARP) inhibitor. - Participant has received prior treatment with any anti-programmed cell death protein (anti-PD-1), or PD Ligand-1 (PD-L1) or PD Ligand-2 (PD-L2) agent or an antibody targeting other immunoregulatory receptors or mechanisms. - Participant has received radiation therapy to lung greater than 30 Gy within 6 months, or antineoplastic biologic therapy within 21 days, or major surgery within 21 days, or tyrosine kinase inhibitor therapy within 7 days, or palliative radiation within 7 days of the first dose of study medication. - Participant has untreated central nervous system (CNS) metastases |
- El participante ha recibido quimioterapia citotóxica previa (incluyendo quimioterapia en combinación con radioterapia) para CPNM, excepto para terapia adyuvante y neoadyuvante acompañada por cirugía con intención curativa completada hasta un año antes del Ciclo 1 Día 2. - El participante ha recibido tratamiento previo con cualquier proteina contra muerte celular programada (anti-PD-1), o ligando de PD 1 (PD-L1) o ligando de PD 2 (PD-L2) o anticuerpo contra otros receptores o mecanismos immunoreguladores. - El participante ha recibido radioterapia al pulmón mayor de 30 Gy hasta un máximo de 6 meses, o terapia biológica antineoplásica hasta un máximo de 21 días, o cirugía mayor hasta un máximo de 21 días, o terapia basada en inhibidores de tirosina-kinasa hasta un máximo de 7 días previos a la primera dosis de la medicación del estudio. - El participante tiene metástasis no tratadas al sistema nervoso central (SNC). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is progression-free survival (PFS). |
La finalidad primaria de eficacia es la supervivencia libre de progresión. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Progression-free survival will be defined as the number of days from the date of randomization to the date of earliest disease progression (radiographic progression per RECIST version 1.1) or death. All events of disease progression will be included, regardless of whether the event occurred while the subject was still taking study drugs or had previously discontinued treatment. If the subject does not experience disease progression or death, then the data will be censored at the date of the subject's last available disease progression assessment (radiographic or clinical). |
La supervivencia libre de progresión es definida como el número de días desde la fecha de aleatorización hasta la fecha de la primera progresión de la enfermedad (progresión radiográfica por RECIST versión 1.1) o muerte. Todos los eventos de progresión de la enfermedad serán incluídos, independientemente de si el evento haya ocurrido mientras el sujeto estuviese en tratamiento con la medicación del estudio o hubiese discontinuado del tratamiento previamente. Si el sujeto no experimenta ninguna progresión de la enfermedad o muerte, los datos serán finalizados a la fecha del último examen (radiográfico o clínico) disponible de progresión de enfermedad del sujeto. |
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints include overall survival, objective response rate, and duration of response. |
Los puntos clave secundarios incluyen el promedio de supervivencia, el ratio de respuesta objetiva, la duración de la respuesta. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Overall survival (OS) will be defined as the number of days from the date of randomization to the date of death
The proportion of subjects with objective response (CR or PR) as assessed by the investigator using RECIST version 1.1 will be evaluated for all dosed subjects (Phase 1 portion) and all randomized subjects (Phase 2 portion).
Duration of overall response (DOR) will be defined as the number of days from the date of first response (CR or PR) to the earliest documentation of radiographic disease progression. |
El promedio de supervivencia es definido como el número de días desde la fecha de la aleatorización hasta la fecha de muerte. La proporción de sujetos con respuesta objetiva (RC o RP) como determinado por el investigador según RECIST versión 1.1 será evaluado para todos los sujetos dosificados (Fase 1) y todos los sujetos aleatorizados (Fase 2). La duración del promedio de respuesta es definida como el número de días desde la fecha de primera respuesta (RP o RC) hasta la primera documentación de progresión radiográfica de la enfermedad. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
dose-escalation to determine RPTD in combination with nivolumab and platinum doublet chemotherapy |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Russian Federation |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |