Resumen del Estudio
Este estudio clínico evalúa la seguridad y eficacia de un medicamento innovador llamado zilovertamab vedotin (MK-2140). Está dirigido a pacientes con ciertos tipos de cáncer de la sangre, como el Linfoma de Células del Manto, la Transformación de Richter, el Linfoma Folicular y la Leucemia Linfocítica Crónica, cuya enfermedad ha regresado (recaída) o no ha respondido a tratamientos anteriores. El objetivo principal es determinar si este fármaco, administrado solo o en combinación con otros agentes, puede reducir el tamaño del tumor y controlar la enfermedad cuando otras opciones terapéuticas se han agotado. Es una oportunidad importante para acceder a terapias dirigidas en un entorno controlado y seguro.
Criterios de Elegibilidad
Resumen de Elegibilidad:Criterios principales: Adultos con diagnóstico confirmado de Linfoma de Células del Manto, Transformación de Richter, Linfoma Folicular o Leucemia Linfocítica Crónica que sean refractarios o hayan recaído tras terapias sistémicas previas. No elegibles: Personas con trasplante de órganos sólidos, problemas cardíacos graves recientes o infecciones activas.
- For aggressive B-cell malignancies mantle cell lymphoma (MCL): Has histologically confirmed biopsy according to the 2016 World Health Organization (WHO) classification of neoplasms of the hematopoietic and lymphoid tissues and has relapsed or refractory disease after at least 2 prior systemic therapies including a Bruton's tyrosine kinase inhibition/inhibitor(s) (BTKi), and is post chimeric antigen receptor T (CAR-T) cell therapy or is ineligible for CAR-T cell therapy.
- For aggressive B-cell malignancies MCL Cohort C: Has histologically confirmed biopsy according to the 2016 World Health Organization (WHO) classification of neoplasms of the hematopoietic and lymphoid tissues and has relapsed or refractory disease after at least 1 prior systemic therapy and has no prior exposure to a non-covalent BTKi.
- For aggressive B-cell malignancies Richter transformation lymphoma (RTL): Has histologically confirmed biopsy according to the 2016 World Health Organization (WHO) classification of neoplasms of the hematopoietic and lymphoid tissues and has relapsed or refractory disease.
- For indolent B-cell malignancies follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL): Has histologically confirmed biopsy and has relapsed or refractory disease after at least 2 prior systemic therapies and no other available therapy.
- Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization/allocation.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 assessed within 7 days before cycle 1 day 1.
- Has received solid organ transplant at any time.
- Has clinically significant (ie, active) cardiovascular disease: cerebral vascular accident/stroke (\<6 months prior to enrollment), myocardial infarction (\<6 months prior to enrollment), unstable angina (\<6 months prior to enrollment), congestive heart failure (New York Heart Association Classification Class ≥II), or serious cardiac arrhythmia requiring medication.
- Has pericardial effusion or clinically significant pleural effusion.
- Has ongoing Grade \>1 peripheral neuropathy.
- Has a demyelinating form of Charcot-Marie-Tooth disease.
- Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
- Participants with FL who have transformed to a more aggressive type of lymphoma.
- Has received prior systemic anticancer therapy within 5 half-lives or 4 weeks (if prior therapy was a monoclonal antibodies) or 2 weeks (if prior therapy was small molecules like kinase inhibitors) prior to the first dose of study intervention.
- Has received prior radiotherapy within 28 days of start of study intervention. Participants must have recovered from all radiation-related toxicities.
- Has ongoing corticosteroid therapy exceeding 30 mg daily of prednisone equivalent.
- Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
- Has known active central nervous system (CNS) lymphoma involvement or active CNS involvement by lymphoma.
- Has an active infection requiring systemic therapy.
- Has a known history of human immunodeficiency virus (HIV) infection not well controlled on antiretroviral therapy (ART)
- Active HBV or hepatitis C virus (HCV) infection.
- For Cohort C only: has any clinically significant gastrointestinal abnormalities that might alter absorption.