E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced and/or metastatic solid tumors |
Tumores sólidos avanzados y/o metastásicos |
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E.1.1.1 | Medical condition in easily understood language |
Solid tumors |
tumores sólidos |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065252 |
E.1.2 | Term | Solid tumor |
E.1.2 | System Organ Class | 100000004864 |
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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 |
Phase 1: To evaluate the safety and tolerability profile of single-agent PRS-344/S095012 To determine the maximum tolerated dose (MTD) if determined, or maximum administered dose (MAD) of PRS-344/S095012
Phase 2: To evaluate the anti-tumor activity and efficacy of PRS-344/S095012, based on appropriate clinical standards for the specified tumor type. |
Fase 1 : -Evaluar el perfil de seguridad y tolerabilidad del agente único PRS-344/S095012 -Determinar la dosis máxima tolerada (DMT) o la dosis máxima administrada (MAD) de PRS-344/S095012
Fase 2: -Evaluar la actividad antitumoral y la eficacia de PRS-344/S095012, basándose en las normas clínicas apropiadas para el tipo de tumor especificado. |
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E.2.2 | Secondary objectives of the trial |
Phase 1: To characterize the pharmacokinetics (PK) of PRS-344/S095012 To evaluate the immunogenicity of PRS 344/S095012 To assess the preliminary anti-tumor activity of PRS-344/S095012 as per RECIST v1.1
Phase 2: To further describe the efficacy, through survival, duration of responses, clinical benefit To further characterize the safety and tolerability of PRS-344/S095012 in specific indications To further characterize the PK profile of PRS-344/S095012 To evaluate those biomarkers potentially predictive of response from tumor and blood samples |
Fase 1 : - Caracterizar la farmacocinética (PK) de PRS-344/S095012 - Evaluar la inmunogenicidad de PRS 344/S095012 - Evaluar la actividad antitumoral preliminar de PRS-344/S095012 según RECIST v1.1.
Fase 2 : - Descripción ampliada de la eficacia, a través de la supervivencia, la duración de las respuestas, el beneficio clínico |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥18 years on the day the consent is signed. 2. Dose escalation and back-fill cohorts: Patients with histologically confirmed diagnosis of unresectable, locally advanced or metastatic solid tumor for which standard treatment options are not available, no longer effective, or not tolerated. 3. Patient should have a documented disease progression on prior therapy before entry into this study. 4. Patients must have at least one measurable target lesion as per RECIST 1.1 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 6. Patient with no available archived material must have one or more tumor lesions amenable to biopsy. 7. Adequate organ function as assessed by laboratory tests within 72 hours prior to the start of treatment.
Dose Expansion: 8. Patients who have had prior checkpoint inhibitor (CPI) treatment in the past 6 months must have documented confirmed radiographic progression from it prior to study entry. 9. Patients with histologically diagnosed extensive stage small cell lung cancer or locally advanced or metastatic squamous cell carcinoma of the esophagus. 10. Patients must have received and progressed on only one prior regimen in the metastatic setting comprising an PD-(L)1 plus chemotherapy. |
1. Edad ≥18 años el día de la firma del consentimiento. 2. Cohortes de escalada de dosis y relleno: Pacientes con diagnóstico histológicamente confirmado de tumor sólido irresecable, localmente avanzado o metastásico para el que las opciones de tratamiento estándar no están disponibles, ya no son eficaces o no se toleran. 3. El paciente debe tener una progresión documentada de la enfermedad con la terapia anterior antes de entrar en este estudio. 4. Los pacientes deben tener al menos una lesión diana medible según RECIST 1.1 5. Estado de rendimiento del Eastern Cooperative Oncology Group (ECOG) de 0 o 1 6. Los pacientes que no dispongan de tejido biopsiado archivado deben tener una o más lesiones tumorales susceptibles de biopsia. 7.Función orgánica adecuada evaluada mediante pruebas de laboratoio en las 72h anteriores al inicio del tratamiento
Expansión de la dosis: 8. Los pacientes que hayan recibido un tratamiento previo con inhibidores de puntos de control (IPC) en los últimos 6 meses deben tener documentada la progresión radiográfica ntes de la entrada en el estudio. 9. Pacientes con cáncer de pulmón de células pequeñas en estadio avanzado diagnosticado histológicamente o carcinoma de células escamosas localmente avanzado o metastásico del esófago. 10. Los pacientes deben haber recibido y progresado con un solo régimen previo en el estadio metastásico que comprenda un PD-(L)1 más quimioterapia. |
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E.4 | Principal exclusion criteria |
1. Patients with previously treated brain metastases may participate provided they are radiologically stable, clinically asymptomatic and are off immunosuppressive therapies for at least 4 weeks. Low dose of steroid<10 mg/day prednisone or equivalent) is allowed 2. Patients who have received prior: a. Small molecule inhibitors, and/or other similar investigational agent: ≤ 2 weeks or 5 half-lives, whichever is shorter. b. Chemotherapy, other monoclonal antibodies, antibody-drug conjugates, or other similar experimental therapies: ≤ 3 weeks or 5 half-lives, whichever is shorter. c. Radioimmunoconjugates or other similar experimental therapies ≤ 6 weeks or 5 half-lives, whichever is shorter. 3. Patients who have received 4-1BB agonists in the past. 4. Patients who had a major surgery within 4 weeks prior to first administration of IMP.
Dose Expansion: 5. Patient who received therapy with an irinotecan containing regimen 6. Patients must not be on warfarin, strong cytochrome P450 (CYP) 3A4 inducers, strong CYP3A4 inhibitors, or strong UGT1A1 inhibitors. |
1. Los pacientes con metástasis cerebrales previamente tratadas pueden participar siempre que estén radiológicamente estables, clínicamente asintomáticos y estén fuera de las terapias inmunosupresoras durante al menos 4 semanas. Se permite una dosis baja de esteroides<10 mg/día de prednisona o equivalente. 2. Pacientes que han recibido previamente: a. Inhibidores de molécula pequeña, y/u otro agente de investigación similar: ≤ 2 semanas o 5 vidas medias, lo que sea más corto. b. Quimioterapia, otros anticuerpos monoclonales, conjugados anticuerpo-fármaco u otras terapias experimentales similares: ≤ 3 semanas o 5 vidas medias, lo que sea más corto. c. Radioinmunoconjugados u otras terapias experimentales similares ≤ 6 semanas o 5 semividas, lo que sea más corto 3. Pacientes que hubieran recibido agonistas 4-1BB en el pasado. 4. Pacientes que hubieran sido intervenidos de cirugía mayor en las 4 semanas previas a la primera administración de IMP
Expansión de dosis: 5. Paciente que haya recibido tratamiento con un régimen conteniendo irinotecan. 6. Los pacientes no deben estar tomando warfarina, inductores potentes del citocromo P450 (CYP) 3A4, inhibidores potentes de CYP3A4 o de UGT1A1. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase 1: Incidence of dose-limiting toxicities (DLTs) Incidence and severity of adverse events (AEs) Discontinuing study treatment due to an AE Laboratory, ECG and vital sign measurements
Phase 2: Objective Response Rate (ORR) : proportion of patients who have Complete Response (CR) or Partial Response (PR) |
Fase 1 : - Incidencia de toxicidades limitantes de la dosis (TLD) - Incidencia y gravedad de los acontecimientos adversos (AA) - Interrupción del tratamiento del estudio debido a un AA - Mediciones de laboratorio, ECG y signos vitales
Fase 2 : - Tasa de respuesta objetiva (ORR): Definida como la proporción de pacientes que tienen Respuesta Completa (RC) o Respuesta Parcial (RP) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
DLT: End of cycle 1 Others: All along the study |
TLD : fin del ciclo 1 Otros : durante todo el estudio |
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E.5.2 | Secondary end point(s) |
Phase 1: Serum PK parameters of PRS-344/S095012 Presence of antidrug antibody (ADA), ORR Duration of Response (DOR): time from first demonstration of response to progression or death, whichever occurs first. Progression-free Survival (PFS): time from the first dose of treatment to first documented disease progression or death due to any cause, whichever occurs first. Overall Survival (OS): time from first dose of study drug to death due to any cause.
Phase2: DCR, DOR, PFS, OS AEs, SAEs, Laboratory, ECG, vital signs Serum PK parameters of PRS-344/S095012 PD-L1, 4-1BB, and CD8 expression in the tumor Tumor mutational burden (TMB), in the tumor and/or blood, MSI status, specific mutations Gene expression profiling in the tumor and/or blood |
Fase 1 : - Parámetros PK de PRS-344/S095012 en suero - Presencia de anticuerpos antifármaco (ADA) , ORR - Duración de la respuesta (DOR): tiempo transcurrido desde la primera demostración de respuesta hasta la progresión o la muerte, lo que ocurra primero. - Supervivencia libre de progresión (SLP): tiempo transcurrido desde la primera dosis de tratamiento hasta la primera progresión documentada de la enfermedad o la muerte por cualquier causa, lo que ocurra primero - Supervivencia global (SG): tiempo transcurrido desde la primera dosis del fármaco del estudio hasta la muerte por cualquier causa.
Fase 2 : - DCR, DOR, PFS, OS - AAs, AAGs, Laboratorio, ECG, signos vitales - Parámetros PK séricos de PRS-344/S095012 - Expresión de PD-L1, 4-1BB y CD8 en el tumor - Carga mutacional del tumor (TMB), en el tumor y/o en la sangre, estado MSI, mutaciones específicas - Perfil de expresión génica en el tumor y/o en la sangre |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All along the study |
Durante todo el estudio |
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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 | No |
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 | Yes |
E.6.10 | Pharmacogenetic | No |
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 | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
First in human - combined phase I/II |
Primero en humano - combinado faseI/II |
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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 | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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 |
Australia |
United States |
Belgium |
France |
Spain |
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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
|
The end of the study is defined as the last patient’s last visit, which includes the long-term safety follow-up visit, 90 days after the last dose of IMP or the last contact attempt if the last participant is declared lost to follow-up. |
El final del estudio se define como la última visita del último paciente, incluida la visita de seguimiento de seguridad, 90 días después de la última dosis del fármaco del estudio o la fecha del último intento de contacto si el paciente se declara perdido para el seguimiento. |
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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 | 2 |
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 | 2 |