Resumen del Estudio
Este ensayo clínico evalúa la seguridad y eficacia de un medicamento en investigación llamado Zilovertamab vedotin (ZV) para pacientes con Linfoma Difuso de Células B Grandes (LDCBG) que ha regresado después del tratamiento o que no ha respondido a las terapias iniciales. El fármaco actúa como un 'misil dirigido' (conjugado anticuerpo-fármaco) diseñado para atacar células cancerosas específicas. El estudio busca determinar si la combinación de Zilovertamab vedotin con un régimen de quimioterapia estándar (R-GemOx: Rituximab, Gemcitabina y Oxaliplatino) ofrece mejores resultados en detener el avance de la enfermedad comparado con la quimioterapia sola. Está dirigido específicamente a pacientes que ya han pasado por tratamientos previos y que no son elegibles o no han tenido éxito con terapias avanzadas como el trasplante de células madre o la terapia CAR-T.
Criterios de Elegibilidad
Resumen de Elegibilidad:Pacientes adultos con diagnóstico confirmado de LDCBG que haya reaparecido o no responda al tratamiento. Deben haber fallado o no ser aptos para trasplante de células madre ni terapia CAR-T. Se requiere buen funcionamiento de órganos. No pueden participar pacientes con VIH, Hepatitis C activa, linfoma activo en el sistema nervioso central o problemas cardíacos graves.
- Has a histologically confirmed diagnosis of Diffuse Large B-Cell Lymphoma (DLBCL).
- Has radiographically measurable DLBCL per the Lugano Response Criteria, as assessed locally by the investigator.
- Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 within 7 days prior to study treatment initiation.
- Has adequate organ function.
- Is able to provide new or archival tumor tissue sample not previously irradiated.
- Has relapsed or refractory DLBCL and is ineligible for or have failed autologous stem-cell transplant (ASCT) and have failed at least 1 line of prior therapy.
- Has post-chimeric antigen receptor T (post-CAR-T) cell therapy failure or is ineligible for CAR-T cell therapy.
- Has relapsed or refractory DLBCL and is ineligible for or have failed ASCT and have failed at least 2 lines of prior therapy.
- Has post-CAR-T therapy failure or is ineligible for CAR-T cell therapy.
- Not applicable with protocol amendment 4: Has history of transformation of indolent disease to DLBCL
- Has received solid organ transplant at any time.
- Has received a diagnosis of primary mediastinal B-cell lymphoma (PMBCL).
- Has clinically significant (ie, active) cardiovascular disease or serious cardiac arrhythmia requiring medication.
- Has ongoing graft-versus-host disease (GVHD) of any grade, or is receiving treatment for their GVHD.
- Has clinically significant pericardial or pleural effusion.
- Has ongoing Grade \>1 peripheral neuropathy.
- Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
- Has a demyelinating form of Charcot-Marie-Tooth disease.
- Has contraindication to any of the study intervention components including but not limited to prior anaphylactic reaction.
- Has received prior systemic anticancer therapy, including investigational agents within 4 weeks prior to the first dose of study intervention.
- Has received prior radiotherapy within 4 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
- Has ongoing corticosteroid therapy.
- Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention.
- Has known active central nervous system (CNS) lymphoma involvement or active CNS involvement by lymphoma. Participants with prior CNS involvement are eligible if their CNS disease is in radiographic, cytological (for cerebrospinal fluid disease), and clinical remission.
- Has an active infection requiring systemic therapy.
- Has a known history of human immunodeficiency virus (HIV) infection.
- Has a known active Hepatitis C virus infection.
- Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.