Estudio de seguridad y eficacia de GEN1046 como agente único o en combinación con pembrolizumab para el tratamiento del cáncer de pulmón (de células no pequeñas) recurrente
Un ensayo de fase 2, multicéntrico, aleatorizado, abierto, de GEN1046 como monoterapia y en terapia combinada con pembrolizumab en sujetos con cáncer de pulmón de células no pequeñas metastásico en recaída/refractario después del tratamiento con la terapia de atención estándar con un inhibidor de punto de control inmunitario
The goal of this clinical trial is to compare the safety and efficacy (how well the drug works) of acasunlimab (also known as GEN1046) when it is used alone (monotherapy) versus when it is combined with a cancer drug (pembrolizumab) for participants with relapsed/refractory (disease has returned after treatment or did not respond to treatment) non-small cell lung cancer (NSCLC; the most common type of lung cancer).
This trial has 2 parts. The purpose of the first part is to find out if the combination of acasunlimab and pembrolizumab is safe and to find out the best doses to use. The purpose of the second part is to give acasunlimab and pembrolizumab to more participants to evaluate efficacy. In the second part of the trial, participants will be randomized to participate in 1 of the 3 arms of the trial. Randomized means that the participant will be randomly assigned to a treatment arm based on chance; no one chooses their treatment arm.
Participants will receive either acasunlimab alone (100 followed by 500 mg into the vein) or acasunlimab with pembrolizumab (200 or 400 mg into the vein) once every 3 or 6 weeks, depending on which arm the participant is randomized into. All participants will receive active drug; no one will receive placebo.
Trial details include:
- The average trial duration for an individual participant will be about 10 months.
- The average treatment duration for an individual participant will be about 6 months.
- The visit frequency will be weekly at first and lessening over time until visits are only once every 3 weeks.
Descripción general del estudio
Estado
Intervención / Tratamiento
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
Contactos y Ubicaciones
Ubicaciones de estudio
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Hanover, Alemania
- Med.Hochschule Hannover Klinik für Pneumologie
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Hessen, Alemania
- Universitatsklinik Giessen und Marburg Standort Giessen
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Immenhausen, Alemania
- LKI Lungenfachklinik Immenhausen
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Regensburg, Alemania
- Department of Internal Medicine II
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Barcelona, España
- Hospital Universitari Vall dHebron
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Madrid, España
- Hospital Universitario 12 de Octubre
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Madrid, España
- MD Anderson Cancer Center
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Madrid, España
- Clinica Universidad de Navarra CUN
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Madrid, España
- Hospital Universitario Fundacion Jimenez Diaz
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Málaga, España
- Hospital Universitario Virgen de la Victoria
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Pamplona, España
- Clinica Universidad de Navarra
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Valencia, España
- Fundacion Instituto Valenciano de Oncologia
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California
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Santa Rosa, California, Estados Unidos, 95403
- St. Joseph Heritage Healthcare
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Florida
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Fort Myers, Florida, Estados Unidos, 33901
- Florida Cancer Specialists - FCS South
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St. Petersburg, Florida, Estados Unidos, 33705
- Florida Cancer Center
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Michigan
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Detroit, Michigan, Estados Unidos, 48202
- Henry Ford Cancer Institute
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Grand Rapids, Michigan, Estados Unidos, 49503
- Cancer & Hematology Centers of Western Michigan CHCWM P.C.
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Wisconsin
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Milwaukee, Wisconsin, Estados Unidos, 53226
- Medical College of Wisconsin
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Bordeaux, Francia
- Institut Bergonie
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Brest, Francia
- Hopital Morvan CHU de Brest
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Rouen, Francia
- Hopital Charles Nicolle Chu Rouen
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Saint-Mandé, Francia
- Hopital dInstruction Des Armees Begin
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Strasbourg, Francia
- Institut de Cancerologie Strasbourg Europe (ICANS)
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Suresnes, Francia
- Hôpital Foch
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Villejuif, Francia
- Gustave Roussy
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Catania, Italia
- Azienda Ospedaliera Universitaria Policlinico G Rodolico San Marco
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Milan, Italia
- IRCCS Istituto Europeo di Oncologia
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Naples, Italia
- UOC Oncoematologia AOU L.Vanvitelli
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Palermo, Italia
- La Maddalena SPA
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Roma, Italia
- IFO Regina Elena
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Amsterdam, Países Bajos
- VU University Medical Center
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Amsterdam, Países Bajos
- Netherlands Cancer Institute
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Leiden, Países Bajos
- Leids Universitair Medisch Centrum
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Rotterdam, Países Bajos
- Erasmus MC
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Olsztyn, Polonia
- Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc
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Warsaw, Polonia
- Maria Sklodowska-Curie National Research Institute of Oncology
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Lisbon, Portugal
- Centro Clinico Champalimaud
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Porto, Portugal
- Centro Hospitalar Universitário do Porto - Hospital de Santo Antonio
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Cheltenham, Reino Unido
- Cheltenham General Hospital
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Manchester, Reino Unido
- The Christie Hospital
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Key Inclusion Criteria:
- Have signed an informed consent form (ICF)
- Be at least 18 years of age.
- Have histologically or cytologically confirmed diagnosis of stage 4 NSCLC with at least 1 prior line of systemic therapy containing an anti-PD-1/PD-L1 mAb for metastatic disease
- Have a tumor PD-L1 expression result available prior to first treatment demonstrating PD-L1 expression in ≥1% of tumor cells as assessed by a central or local laboratory during screening.
- Have measurable disease per RECIST v1.1.
- Have Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1.
- Have life expectancy of at least 3 months.
- Have adequate organ and bone marrow function as defined in the protocol.
Key Exclusion Criteria:
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Documentation of known EGFR, KRAS, RET, ROS1, BRAF mutations, NTRK gene infusions, RET arrangement, ALK gene rearrangements, high-level MET amplification, or METex 14 skipping. Note: Subjects harboring such mutations, gene rearrangements or amplifications may be enrolled in the trial, if subjects have received prior approved targeted therapy for such mutations, the subject may still be eligible for this trial.
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Treatment with an anti-cancer agent within 28 days prior to acasunlimab administration.
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Any investigational agent (including investigational vaccines).
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Radiotherapy within 14 days prior to first dose of acasunlimab. Note: palliative radiotherapy will be allowed for local pain control under certain conditions.
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Chronic systemic immunosuppressive corticosteroid doses, ie, prednisone >10 mg daily or a cumulative dose >150 mg prednisone within 14 days before the first acasunlimab administration.
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Subject has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
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Subject has contraindications to the use of pembrolizumab per local prescribing information.
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Subject has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis (interstitial lung disease).
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Ongoing or active infection requiring intravenous treatment with anti-infective therapy or any ongoing systemic inflammatory condition requiring further diagnostic work-up or management during screening.
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Symptomatic congestive heart failure (grade III or IV as classified by the New York Heart Association), unstable angina pectoris, or cardiac arrhythmia.
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Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg, despite optimal medical management.
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Ongoing or recent (within 6 months) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for irAEs.
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Subject has a known history of any of the following:
- Grade 3 or higher irAEs that led to treatment discontinuation of a prior immunotherapy treatment.
- Myositis, Guillain-Barré syndrome, or myasthenia gravis of any grade.
- Liver disease (eg, alcoholic hepatitis or non-alcoholic steatohepatitis, drug-related or autoimmune hepatitis, or evidence of hepatic cirrhosis).
- Organ allograft (except for corneal transplant) or autologous or allogeneic bone marrow transplant, or stem cell rescue within 3 months prior to the first dose of acasunlimab.
- Grade 3 or higher allergic reactions to monoclonal antibody therapy as well as known or suspected allergy or intolerance to any agent given in the course of this trial.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: Arm A
Treatment with acasunlimab once every 21 days for the first 2 cycles and then every 42 days in subsequent cycles |
Acasunlimab will be administered intravenously (IV)
Otros nombres:
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Experimental: Arm B
Treatment with acasunlimab + pembrolizumab once every 21 days |
Acasunlimab will be administered intravenously (IV)
Otros nombres:
Pembrolizumab will be administered IV
Otros nombres:
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Experimental: Arm C
Treatment with acasunlimab + pembrolizumab once every 42 days |
Acasunlimab will be administered intravenously (IV)
Otros nombres:
Pembrolizumab will be administered IV
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Objective response rate (ORR)
Periodo de tiempo: From first treatment to approximately 27 weeks after last subject's first dose
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ORR will be measured as the proportion of subjects with a confirmed response of complete response (CR) or partial response (PR) as per RECIST v1.1 |
From first treatment to approximately 27 weeks after last subject's first dose
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Duration of response (DOR)
Periodo de tiempo: From onset date of response until disease progression/death/lost to follow-up/start of new anticancer therapy or withdrawal of consent, whichever occurs first (an expected average of 6 months)
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DOR will be measured as the time from initial onset of CR or PR to first radiographic progression as per RECIST v. 1.1 or death from any cause, whichever occurs first. |
From onset date of response until disease progression/death/lost to follow-up/start of new anticancer therapy or withdrawal of consent, whichever occurs first (an expected average of 6 months)
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Time to response (TTR)
Periodo de tiempo: From first treatment to date of onset of initial response (CR or PR) as per RECIST v.1.1 (an expected average of 6 months)
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TTR will be measured as the time from first treatment to onset of initial response (CR or PR) as per RECIST v.1.1 |
From first treatment to date of onset of initial response (CR or PR) as per RECIST v.1.1 (an expected average of 6 months)
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Progression-free survival (PFS)
Periodo de tiempo: From first treatment to first documented progression or death due to any cause (an expected average of 6 months)
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PFS will be measured from date of first treatment until date of radiographic progression as per RECIST v.1.1 or until death from any cause, whichever occurs first |
From first treatment to first documented progression or death due to any cause (an expected average of 6 months)
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Overall survival (OS)
Periodo de tiempo: From first treatment to date of death (assessed up to 3 years after the last participant's first dose in the trial)
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Defined as time to death from of any cause |
From first treatment to date of death (assessed up to 3 years after the last participant's first dose in the trial)
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Incidence and severity of adverse events (AEs) and laboratory abnormalities
Periodo de tiempo: Throughout the trial until end of safety follow-up period (60 days or 90 days after last dose)
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Incidence of treatment-emergent AEs as assessed by CTCAE v5.0. Laboratory parameters graded by CTCAE v5.0 |
Throughout the trial until end of safety follow-up period (60 days or 90 days after last dose)
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Director de estudio: Study Official, Genmab
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
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
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- GCT1046-04
- 2021-001928-17 (Número EudraCT)
- 1004314 (Otro identificador: IRAS ID; UK Research Summaries Database)
- NL-OMON54259 (Identificador de registro: CCMO (The Netherlands))
- 2024-513770-22-00 (Otro identificador: EU Trial (CTIS) Number)
- RECF-005102 (Identificador de registro: National Institute of Cancer France)
- 15582 (Identificador de registro: Portugal RNET)
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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