Estudio de plataforma para evaluar la seguridad y la eficacia de múltiples combinaciones de tratamientos en pacientes con mieloma múltiple

1. ¿Por qué es necesario el ensayo clínico CO43923?

El mieloma múltiple (MM) es un tipo de cáncer de la médula ósea. Un fármaco llamado lenalidomida funciona bien en personas con MM menos agresivo (riesgo bajo/intermedio) cuando se utiliza después de un trasplante de células madre, lo que se conoce como tratamiento de «mantenimiento». Sin embargo, se necesitan nuevos tratamientos de mantenimiento para las personas a las que se ha diagnosticado una forma agresiva (de alto riesgo) de MM. 

Los investigadores esperan que el uso de lenalidomida en combinación con fármacos diseñados para ayudar al propio sistema inmunitario de la persona a atacar y destruir las células cancerosas, como el cevostamab, logre mejores resultados de salud en las personas con MM de alto riesgo después de un trasplante.

2. ¿EN QUÉ CONSISTE EL ENSAYO CLÍNICO CO43923?

En este ensayo clínico se están inscribiendo personas que tienen una enfermedad llamada MM. Las personas pueden participar si se les ha diagnosticado MM de alto riesgo que ha respondido previamente al tratamiento y han recibido un trasplante. 

El objetivo de este ensayo clínico es evaluar la seguridad y la eficacia del cevostamab en combinación con lenalidomida y el modo en que el cuerpo procesa estos fármacos.

Los participantes recibirán el tratamiento del ensayo clínico, cevostamab, en un hospital a diferentes intervalos a lo largo de todo el ensayo durante 13 períodos de tratamiento (también llamados “ciclos”) y cada ciclo durará 28 días. Los participantes también recibirán lenalidomida a diario durante 21 días en ciclos de 28 días hasta que su enfermedad empeore o hasta que interrumpan el tratamiento por efectos secundarios.  

El médico del ensayo clínico verá a los participantes a diferentes intervalos durante todo el ensayo clínico. En estas visitas al hospital se realizarán evaluaciones para comprobar la respuesta del participante al tratamiento y detectar los posibles efectos secundarios que pueda presentar. Después de la última dosis, los participantes serán atendidos por el médico del ensayo clínico aproximadamente cada 3 meses en el hospital o por teléfono mientras estén de acuerdo. La participación en el ensayo clínico durará en total entre 3 y 5 años aproximadamente. Los participantes tendrán libertad para interrumpir el tratamiento del ensayo y abandonar el ensayo clínico en cualquier momento.

3. ¿Cuáles son los principales criterios de valoración del ensayo clínico CO43923?

El criterio de valoración principal del ensayo clínico (los principales resultados que se miden en el ensayo para comprobar si el medicamento ha funcionado) consiste en evaluar la seguridad del cevostamab en combinación con lenalidomida, lo que se determinará mediante el número y el tipo de efectos secundarios que presenten los participantes. 

Los otros criterios de valoración del ensayo clínico son el porcentaje de participantes sin cáncer detectable o con una disminución del tamaño del cáncer de al menos el 50 % en comparación con el comienzo del ensayo (tasa de respuesta objetiva) y el tiempo que los participantes siguen con vida (supervivencia global).

4. ¿Quién puede participar en este ensayo clínico?

Podrán participar en este ensayo las personas que tengan al menos 18 años, se les haya diagnosticado un MM de alto riesgo, hayan recibido previamente un trasplante en los últimos 100 días y todavía no hayan empezado el tratamiento de mantenimiento.  

No podrán participar en este ensayo las personas que hayan recibido tratamiento previo con cevostamab, que padezcan determinadas enfermedades, que hayan recibido previamente determinados tratamientos, que estén embarazadas o en período de lactancia o que tengan previsto quedarse embarazadas.

5. ¿Qué tratamiento recibirán los participantes en este ensayo clínico? 

Se trata de un ensayo sin enmascaramiento, lo que significa que todas las personas que intervienen, incluidos los participantes y los médicos, saben cuál es el fármaco del ensayo clínico que se está utilizando. Todos los participantes en este ensayo clínico recibirán cevostamab en combinación con lenalidomida en ciclos de 28 días y después lenalidomida sola (en monoterapia) en ciclos de 28 días:

• En el ciclo 1, los participantes recibirán dosis escalonadas (crecientes) de cevostamab en forma de infusión intravenosa los días 1, 8 y 15 (la dosis deseada recomendada se alcanzará el día 15).
• Entre los ciclos 2 y 6, los participantes recibirán cevostamab mediante infusión intravenosa los días 1 y 15 en la dosis deseada y, posteriormente, una vez cada 28 días entre los ciclos 7 y 13.
• Durante los ciclos 1–13 y en adelante, los participantes recibirán lenalidomida en forma de cápsulas que se tragarán una vez al día los días 1‒21 de cada ciclo de 28 días.

La finalidad de la dosis escalonada es prevenir o reducir los efectos secundarios. Si un participante presenta un efecto secundario denominado «síndrome de liberación de citoquinas» (cuando las células inmunitarias del cuerpo se activan y liberan grandes cantidades de sustancias inflamatorias por todo el cuerpo), podría recibir otro fármaco llamado tocilizumab.

1. Why is the CO43923 SS2 clinical trial needed?

Multiple myeloma (MM) is a cancer that forms in plasma cells (a type of white blood cell that is made in the bone marrow). People diagnosed with MM are first treated with a combination of anti-cancer drugs. This is often followed by a stem cell transplant that aims to replace the abnormal bone marrow. After the stem cell transplant, maintenance therapy (to help stop cancer coming back) with lenalidomide is considered the standard treatment for most people diagnosed with MM. However, new treatments are needed for when the MM is difficult to remove completely (high-risk MM) because lenalidomide does not work as well in these situations.

Cevostamab is a type of drug called a bispecific antibody. It works by binding to certain proteins on the cancer cells and cells of the immune system to bring them closer together, which helps the body destroy the cancer. Drugs like cevostamab, a type of immunotherapy, help a person’s own immune system target cancer cells. Researchers hope that they will provide better health outcomes for people with high-risk MM after a transplant.

This clinical trial aims to test how safe and how well cevostamab in combination with lenalidomide works, and how the body processes these drugs.

2. How does the CO43923 SS2 clinical trial work?

This clinical trial is recruiting people with MM. People can take part if they have been diagnosed with high-risk MM that has previously responded to treatment and have received a transplant.

People who take part in this clinical trial (participants) will be given the clinical trial treatment cevostamab in a hospital for 14 treatment ‘cycles’ – a treatment cycle is the period of treatment and recovery time before the next dose of treatment is given. Participants will also be given lenalidomide until their disease worsens or until they stop treatment due to side effects. The clinical trial doctor will see them regularly; these hospital visits will include checks to see how the participant responds to the treatment and any side effects they may have. After their final dose, participants will be seen by the clinical trial doctor around every 3 months at the hospital or by telephone for as long as they agree. The total time of participation in the clinical trial will be about 1 year or more. Participants are free to stop trial treatment and leave the clinical trial at any time.

3. What are the main endpoints of the CO43923 SS2 clinical trial?

The main clinical trial endpoints (the main results measured in the trial to see how safe treatment is) are the number, type and seriousness of side effects and the maximum dose of cevostamab that can be given with lenalidomide before participants have unacceptable side effects.

The other clinical trial endpoints include:

• The number of participants whose response to treatment improves
• The amount of time between the start of the trial treatment and participants’ cancer worsening
• The number of participants who have no detectable cancer in bone marrow or on blood tests, or at least 90% reduction in cancer on blood tests
• How long participants live
• How the body processes and gets rid of cevostamab and lenalidomide

4. Who can take part in this clinical trial?

People can take part in this trial if they are at least 18 years old, have been diagnosed with high-risk MM, have previously received a transplant within the past 100 days and have not yet started maintenance treatment.

People may not be able to take part in this trial if they have certain other medical conditions, such as autoimmune, heart or lung disease, or certain infections, have previously received certain treatments, including cevostamab, are pregnant or breastfeeding, or are planning to become pregnant during or within 5 months of treatment.

5. What treatment will participants be given in this clinical trial?

Everyone who joins this clinical trial will be given cevostamab and lenalidomide. To begin, participants will be given step-up (increasing) doses of cevostamab over 2 weeks; as an infusion into the vein on Days 1 and 4, with the target dose given on Day 8. Step-up dosing aims to prevent and/or reduce side effects.

Treatment will then be provided in 28-day treatment cycles, where participants will be given:

• Cevostamab, as an infusion into the vein on Days 1 and 15 in Cycles 1‒6, then on Day 1 only in Cycles 7‒13
• Lenalidomide, as a capsule to be swallowed once a day on Days 1‒21 of every cycle

Participants may also receive tocilizumab as an infusion into the vein if they experience certain side effects during the clinical trial.

This is an open-label trial, which means everyone involved, including the participants and the doctors, know which clinical trial drug is being used.

6. Are there any risks or benefits in taking part in this clinical trial?

The safety or effectiveness of the experimental treatment or use may not be fully known at the time of the trial. Most trials involve some risks to the participant. However, it may not be greater than the risks related to routine medical care or the natural progression of the health condition. People who would like to participate will be told about any risks and benefits of taking part in the clinical trial, as well as any additional procedures, tests or assessments they will be asked to undergo. All of these will be described in an informed consent document (a document that provides people with the information they need to decide to volunteer for the clinical trial).

Risks associated with the clinical trial drugs

Participants may have side effects (an unwanted effect of a drug or medical treatment) from the drugs used in this clinical trial. Side effects can be mild to severe and even life-threatening and vary from person to person. Participants will be closely monitored during the clinical trial; safety assessments will be performed regularly. Potential participants will be told about the known side effects of cevostamab, tocilizumab and lenalidomide and, where relevant, also potential side effects based on human and laboratory studies or knowledge of similar drugs. Participants will be told about any known side effects of infusions into the vein (intravenous infusions) or of swallowing capsules.

Potential benefits associated with the clinical trial

Participants' health may or may not improve from participation in the clinical trial, but the information that is collected may help other people who have a similar medical condition in the future.

1. Why is the CO43923 SS4 clinical trial needed?

Multiple myeloma (MM) is a cancer that forms in plasma cells – a type of white blood cell that is made in the bone marrow. Different types of medicines are given as standard-of-care treatment depending on the type of MM a person has. This includes protease inhibitors (PIs) or medicines that help a person’s own immune system target and destroy cancer cells – known as ‘immunotherapy’ (such as IMiDs or anti-CD38 drugs). But for most people, MM eventually comes back after treatment or does not respond to treatment (known as ‘relapsed/refractory’ or ‘R/R’ MM).

Cevostamab and iberdomide are new experimental drugs against MM – this means that health authorities have not approved cevostamab or iberdomide for the treatment of R/R MM, alone or in combination with each other. Although cevostamab and iberdomide have not been given together to people before, researchers hope that combined cevostamab and iberdomide treatment will improve health outcomes for people with R/R MM.

This clinical trial aims to see how safe and how well cevostamab in combination with iberdomide works, and how the body processes these drugs.

2. How does the CO43923 SS4 clinical trial work?

This clinical trial is recruiting people with R/R MM. People can take part if they have previously received a PI, an IMiD and an anti-CD38 medicine, and have no standard-of-care treatment options available to them. 

People who take part in this clinical trial (participants) will be given the clinical trial treatment cevostamab in a hospital at different intervals throughout the trial for 18 treatment ‘cycles’ – a treatment cycle is the period of treatment and recovery time before the next dose of treatment is given. Participants will also be given iberdomide. Treatment will be stopped if MM worsens or if participants have unacceptable side effects. If their MM worsens after 18 cycles, participants who benefitted from treatment may be given up to 17 more cycles of treatment.

The clinical trial doctor will see participants regularly. These hospital visits will include checks to see how the participant responds to the treatment and any side effects they may have. After their final dose, participants will be seen by the clinical trial doctor around every 3 months at the hospital or by telephone for as long as they agree. The total time of participation in the clinical trial will depend on how the participant responds to treatment and could be more than 3 years. Participants are free to stop trial treatment and leave the clinical trial at any time.

3. What are the main endpoints of the CO43923 SS4 clinical trial?

The main clinical trial endpoints (the main results measured in the trial to see how safe treatment is) are the number, type and seriousness of side effects and the maximum doses of cevostamab and iberdomide that can be given together before participants have unacceptable side effects. 

The other clinical trial endpoints include: 

• The number of participants whose tumours shrink with trial treatment and the amount of time this lasts if disease progresses
• The number of participants who have no detectable cancer in bone marrow or on blood tests, or at least 90% reduction in cancer on blood tests
• The amount of time between the start of the trial treatment and participants’ cancer worsening 
• The amount of time taken to first respond to treatment and to the best response seen to treatment in participants with at least a 50% reduction in cancer
• How long participants live
• How the body processes and gets rid of trial treatment

4. Who can take part in this clinical trial?

People with R/R MM can take part in this trial if they are at least 18 years old. People may not be able to take part in this trial if they have certain other medical conditions, such as autoimmune, heart or lung disease, uncontrolled high blood pressure or diabetes, or certain infections. 

People who have previously received certain treatments including cevostamab, who are pregnant or breastfeeding, or who are planning to become pregnant during or shortly after the trial, will also not be able to take part.

5. What treatment will participants be given in this clinical trial?

Everyone who joins this clinical trial will be given cevostamab and iberdomide. To begin, participants will be given step-up (increasing) doses of cevostamab over 2 weeks as an infusion into the vein on Days 1 and 4, with the target dose given on Day 8. Step-up dosing aims to prevent and/or reduce side effects. Treatment will then be provided in 21-day cycles, where participants will be given:

• Cevostamab, as an infusion into the vein on Day 1, AND 
• Iberdomide, as a capsule to be swallowed once a day on Days 1‒14 of each cycle

Participants may also receive tocilizumab as an infusion into the vein if they experience certain side effects during the clinical trial. This is an open-label trial, which means everyone involved, including the participants and the doctors, know which clinical trial drug is being used.

6. Are there any risks or benefits in taking part in this clinical trial?

The safety or effectiveness of the experimental treatment or use may not be fully known at the time of the trial. Most trials involve some risks to the participant. However, it may not be greater than the risks related to routine medical care or the natural progression of the health condition. People who would like to participate will be told about any risks and benefits of taking part in the clinical trial, as well as any additional procedures, tests or assessments they will be asked to undergo. All of these will be described in an informed consent document (a document that provides people with the information they need to decide to volunteer for the clinical trial). 

Risks associated with the clinical trial drugs

Participants may have side effects (an unwanted effect of a drug or medical treatment) from the drugs used in this clinical trial. Side effects can be mild to severe and even life-threatening and vary from person to person. Participants will be closely monitored during the clinical trial; safety assessments will be performed regularly. Potential participants will be told about the known side effects of cevostamab, iberdomide and tocilizumab and, where relevant, also potential side effects based on human and laboratory studies or knowledge of similar drugs. Participants will be told about any known side effects of infusions into the vein (intravenous infusions) or of swallowing capsules.

Potential benefits associated with the clinical trial

Participants' health may or may not improve from participation in the clinical trial, but the information that is collected may help other people who have a similar medical condition in the future.

6. ¿Existe algún riesgo o beneficio por participar en este ensayo clínico?

Es posible que, en el momento del ensayo, no se conozca por completo la seguridad o la eficacia del tratamiento experimental o su uso. La mayoría de los ensayos suponen ciertos riesgos para los participantes, aunque pueden no ser mayores que los riesgos relacionados con la asistencia médica habitual o la progresión natural de la enfermedad. Se informará a los posibles participantes de los riesgos y beneficios de participar en el ensayo clínico, así como de los de cualquier procedimiento, prueba o evaluación adicional a los que se les pida que se sometan. Todo ello se describirá en un documento de consentimiento informado (documento en el que se facilita a las personas la información que necesitan para tomar una decisión respecto a si desean participar de forma voluntaria en un ensayo clínico). Los posibles participantes también deberían comentar los riesgos y posibles beneficios con los miembros del equipo investigador y con su profesional sanitario habitual. Las personas que estén interesadas en participar en un ensayo clínico deben conocer todo lo posible respecto al ensayo y sentirse cómodas para hacer cualquier pregunta sobre el ensayo al equipo investigador.

Riesgos asociados a los fármacos del ensayo clínico 

Los participantes pueden sufrir efectos secundarios (efectos no deseados de un fármaco o un tratamiento médico) con los fármacos utilizados en este ensayo clínico. Los efectos secundarios pueden ser desde leves hasta graves e incluso poner en peligro la vida, y pueden variar en cada persona.  

Cevostamab, tocilizumab y lenalidomida 

Se informará a los posibles participantes de los efectos secundarios conocidos del cevostamab, el tocilizumab y la lenalidomida y, cuando proceda, también de los efectos secundarios potenciales según los estudios realizados en seres humanos y de laboratorio o los conocimientos sobre fármacos similares. 

El cevostamab y el tocilizumab se administrarán mediante infusión intravenosa (en una vena). Se informará a los participantes de los efectos secundarios conocidos de la administración intravenosa. 

La lenalidomida se administrará en cápsulas orales (para tragar). Se informará a los participantes de los efectos secundarios conocidos de la administración oral. 

Posibles beneficios asociados al ensayo clínico 

No es seguro que la salud de los participantes vaya a mejorar por participar en el ensayo clínico, pero la información que se obtenga podría ayudar en el futuro a otras personas con enfermedades parecidas. 

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Si desea obtener más información sobre este ensayo clínico, consulte la pestaña For Expert en la página ForPatients específica o siga este enlace de ClinicalTrials.gov  https://clinicaltrials.gov/ct2/show/NCT05583617