| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Relapsed or Refractory Multiple Myeloma (RRMM) |
| Mieloma múltiple recidivante o resistente (MMRR) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Cancer of plasma cells |
| Cancer de células plasmáticas |
|
| 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 | 10067095 |
| E.1.2 | Term | Multiple myeloma progression |
| E.1.2 | System Organ Class | 100000004864 |
|
| 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 |
To determine the safety and tolerability of CC-92480 and dexamethasone in combination with tazemetostat, BMS-986158, or trametinib in participants with RRMM.
To define the RP2D and schedule of each combination in participants with RRMM. |
Determinar la seguridad y tolerabilidad de CC-92480 y dexametasona en combinación con tazemetostat, BMS-986158 o trametinib en participantes con MMRR.
Definir la DRF2 y la pauta de cada combinación en participantes con MMRR |
|
| E.2.2 | Secondary objectives of the trial |
To evaluate the preliminary efficacy of CC-92480 in novel combinations compared against control (CC-92480 + dexamethasone) in participants with RRMM.
To characterize the pharmacokinetics of CC-92480 when administered in combination with tazemetostat, BMS-986158, or trametinib. |
Evaluar la eficacia preliminar de CC-92480 en combinaciones innovadoras en comparación con el grupo control (CC-92480 + dexametasona) en participantes con MMRR.
Caracterizar la farmacocinética de CC-92480 cuando se administra en combinación con tazemetostat, BMS-986158 o trametinib. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Participants are eligible to be included in the study only if all of the following criteria apply:
1. Signed written informed consent prior to any study procedure.
2. ≥ 18 years of age the time of signing the ICF.
3. Relapsed or refractory multiple myeloma (MM) and must:
a. have documented disease progression during or after their last myeloma therapy
b. be refractory to, intolerant to, or not a candidate for available, established therapies known to provide clinical benefit in MM
4. Must have measurable disease.
5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
6. Agree to follow the CC-92480 Pregnancy Prevention Plan (PPP) |
Los participantes son elegibles para ser incluidos en el estudio solo si se aplican todos los siguientes criterios:
1. Consentimiento informado por escrito firmado antes de cualquier procedimiento de estudio.
2. ≥ 18 años cumplidos en el momento de la firma del ICF.
3. El participante tiene antecedentes de MM con enfermedad recidivante o resistente y debe:
a) Tener progresión de la enfermedad documentada en base a los criterios uniformes de respuesta del Grupo de Trabajo Internacional del Mieloma (International Myeloma Working Group, IMWG) durante o después de su último tratamiento para el mieloma
b) Ser refractario, intolerante o no ser candidato para los tratamientos disponibles establecidos que se conoce que ofrecen beneficio clínico en MM.
4. Los participantes deben tener enfermedad medible
5. El participante presenta un estado funcional según el Grupo Oncológico Cooperativo del Este de Estados Unidos (Eastern Cooperative Oncology Group, ECOG) de 0 o 1.
6. Aceptar seguir el Plan de Prevención de Embarazo (PPP) de CC-92480 |
|
| E.4 | Principal exclusion criteria |
Participants are excluded from the study if any of the following criteria apply:
1. Known active or history of central nervous system (CNS) involvement of MM.
2. Plasma cell leukemia; Waldenstrom’s macroglobulinemia; polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome; or clinically significant light-chain amyloidosis.
3. Impaired cardiac function or clinically significant cardiac disease.
4. Participant has previous SARS-CoV-2 infection within 14 days for asymptomatic or mild symptomatic infections or 28 days for severe/critical illness prior to Cycle 1 Day 1 (C1D1)
5. For Part 1: received prior therapy with CC-92480.
6. For Part 2: received prior therapy with CC-92480, tazemetostat, BMS-986158, or trametinib.
7. Previously received allogeneic stem-cell transplant at any time or received autologous stem-cell transplant within 12 weeks of initiating study treatment
8. Received any of the following within 14 days prior to initiating study treatment:
a. Plasmapheresis
b. Major surgery
c. Radiation therapy other than local therapy for myeloma associated bone lesions
d. Use of any systemic anti-myeloma drug therapy
9. Used any investigational agents within 28 days or 5 half-lives (whichever is shorter) prior to initiating study treatment.
10. COVID-19 vaccine within 14 days prior to C1D1 |
Los participantes quedan excluidos del estudio si se aplica alguno de los siguientes criterios:
1. Compromiso activo conocido o antecedentes de compromiso del sistema nervioso central (SNC) de MM.
2. Leucemia de células plasmáticas; macroglobulinemia de Waldenstrom; síndrome de polineuropatía, organomegalia, endocrinopatía, proteína M y cambios en la piel (POEMS); o amiloidosis de cadena ligera clínicamente significativa.
3. Deterioro de la función cardíaca o enfermedad cardíaca clínicamente significativa.
4. El participante tiene una infección previa por SARS-CoV-2 dentro de los 14 días para infecciones asintomáticas o sintomáticas leves o 28 días para enfermedades graves/críticas antes del ciclo 1, día 1 (C1D1)
5. Para la Parte 1: recibió terapia previa con CC-92480.
6. Para la Parte 2: recibió tratamiento previo con CC-92480, tazemetostat, BMS-986158 o trametinib.
7. Recibió previamente un alotrasplante de células madre en cualquier momento o recibió un autotrasplante de células madre dentro de las 12 semanas posteriores al inicio del tratamiento del estudio.
8. Recibió cualquiera de los siguientes dentro de los 14 días anteriores al inicio del tratamiento del estudio:
a) Plasmaféresis
b) Cirujía importante
c) Radioterapia distinta de la terapia local para lesiones óseas asociadas al mieloma
d) Uso de cualquier tratamiento farmacológico antimieloma sistémico
9. Usó cualquier agente en investigación dentro de los 28 días o 5 vidas medias (lo que sea más corto) antes de iniciar el tratamiento del estudio.
10. Vacuna COVID-19 dentro de los 14 días anteriores a C1D1 |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Safety : Type, frequency, seriousness, and severity of adverse events (AEs), and relationship of AEs to study treatment.
Recommended Phase 2 Dose (RP2D):
Establish the RP2D for CC-92480 in each novel treatment combination with dexamethasone. |
Seguridad: tipo, frecuencia, gravedad y severidad de los eventos adversos (EA) y relación de los EA con el tratamiento del estudio.
Dosis recomendada de fase 2 (RP2D):
Establecer el RP2D para CC-92480 en cada nueva combinación de tratamiento con dexametasona. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
safety is reviewed continuously during the study, no specific timepoint.
I would also say continuously during the study. RP2D is strictly speaking defined in Part 1 but is confirmed during part 2. |
La seguridad se revisa continuamente durante el estudio, sin un punto de tiempo específico.
También diría continuamente durante el estudio. RP2D se define estrictamente en la Parte 1, pero se confirma durante la Parte 2. |
|
| E.5.2 | Secondary end point(s) |
Overall Response Rate (ORR) :
Best response ≥ partial response (PR), according to the International Myeloma Working Group (IMWG) Uniform Response Criteria89
Complete Response Rate (CRR):
Percentage of participants who achieved
≥ complete response (CR), according to
IMWG Uniform Response Criteria
 Very Good Partial Response Rate
(VGPRR) :
Percentage of participants who achieved
≥ VGPR, according to IMWG Uniform
Response Criteria
Progression-Free Survival (PFS) :
Time from enrollment to the first
documentation of progressive disease (PD) or death from any cause during study, whichever occurs earlier
Time-to-Response (TTR) :
Time from first dose to the first
documentation of response (≥ PR)
Duration of Response (DOR) :
Time from the first documentation of
response (≥ PR) to the first documentation of PD or death |
Tasa de respuesta general (TRG):
Mejor respuesta ≥ respuesta parcial (RP), según los Criterios de respuesta uniforme del Grupo de Trabajo Internacional sobre Mieloma (IMWG)89
Tasa de respuesta completa (TRC):
Porcentaje de participantes que lograron
≥ respuesta completa (RC), según
Criterios de respuesta uniforme del IMWG
Muy buena tasa de respuesta parcial
(VGPRR) :
Porcentaje de participantes que lograron
≥ VGPR, según IMWG Uniform
Criterios de respuesta
Supervivencia libre de progresión (SLP):
Tiempo desde la inscripción hasta la primera
documentación de enfermedad progresiva (EP) o muerte por cualquier causa durante el estudio, lo que ocurra primero
Tiempo de respuesta (TTR):
Tiempo desde la primera dosis hasta la primera
documentación de respuesta (≥ PR)
Duración de la respuesta (DOR):
Tiempo desde la primera documentación de
respuesta (≥ PR) a la primera documentación de DP o muerte |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| every cycle up to cycle 12 and every other cycle after that |
| cada ciclo hasta el ciclo 12 y cada dos ciclos después de ese |
|
| 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 | 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 | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
| Dose finding |
| Busqueda de dosis |
|
| 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 | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| 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 | 3 |
| 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 |
| Canada |
| United States |
| Spain |
| Norway |
| United Kingdom |
|
| 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
|
| LVLS |
| Ultima visita del último sujeto |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | 1 |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 1 |
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