Resumen

The purpose of this Phase 2/3, randomized, multisite, open-label, dose confirmation, and expansion study is to evaluate the safety, and efficacy of zilovertamab vedotin (ZV) in combination with standard of care options for the treatment of rrDLBCL. This study will be divided into 2 parts: Dose Confirmation (Part 1) and Efficacy Expansion (Part 2) and will enroll participants who are at least 18 years of age with rrDLBCL. The hypotheses are: ZV in combination with rituximab, gemcitabine, and oxaliplatin (R-GemOx) is superior to R-GemOx with respect to progression-free survival (PFS) per Lugano response criteria by blinded independent review committee (BICR); and that ZV in combination with bendamustine rituximab (BR) is superior to BR with respect to PFS per Lugano response criteria by BICR. With protocol amendment 4 (effective: 04-April-2024), enrollment in Cohort B (study arms Bendamustine Rituximab \[BR\] and ZV + BR) is discontinued. No efficacy outcome analysis and hypothesis testing will be conducted for Cohort B.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

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.
Zilovertamab vedotin plus R-GemOx, or R-GemOx study arms:
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.
Not applicable with protocol amendment 4: Zilovertamab vedotin plus Bendamustine Rituximab (BR), and Bendamustine Rituximab study arms:
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.

Criterios de exclusión

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.

Intervenciones

biological

Zilovertamab vedotin

Intravenous (IV) Infusion 1.5 mg/kg, 1.75 mg/kg, 2.0 mg/kg, 2.25 mg/kg, 2.5 mg/kg

biological

Rituximab

IV Infusion 375 mg/m\^2

drug

Gemcitabine

IV Infusion 1000 mg/m\^2

drug

Oxaliplatin

IV Infusion 100 mg/m\^2

drug

Bendamustine

IV Infusion 90 mg/m\^2

drug

Granulocyte Colony-Stimulating Factor (G-CSF)

Prophylactic G-CSF will be administered at each cycle of zilovertamab vedotin as per the institutional guidelines.

Ubicaciones

Hospital Italiano de Buenos Aires ( Site 2203)

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

Study Coordinator · +541149590200

RECRUITING

Instituto de Investigaciones Clínicas Mar del Plata ( Site 2205)

Mar del Plata, Buenos Aires, Argentina

Study Coordinator · +542234963224

RECRUITING

Hospital Aleman ( Site 2200)

Buenos Aites, Buenos Aires F.D., Argentina

Study Coordinator · +541148277000

RECRUITING

Hospital Privado Universitario de Córdoba ( Site 2202)

Córdoba, Córdoba Province, Argentina

Study Coordinator · +543514688200

RECRUITING

Instituto Alexander Fleming ( Site 2201)

CABA, Argentina

Study Coordinator · +541132218900

RECRUITING

A Phase 2/3 Multicenter, Open-label, Randomized, Active-Control Study of Zilovertamab Vedotin (MK-2140) in Combination With Standard of Care in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (waveLINE-003)

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Zilovertamab vedotin

Rituximab

Gemcitabine

Oxaliplatin

Bendamustine

Granulocyte Colony-Stimulating Factor (G-CSF)

Ubicaciones

Hospital Italiano de Buenos Aires ( Site 2203)

Instituto de Investigaciones Clínicas Mar del Plata ( Site 2205)

Hospital Aleman ( Site 2200)

Hospital Privado Universitario de Córdoba ( Site 2202)

Instituto Alexander Fleming ( Site 2201)

Patrocinadores

Contactos

Toll Free Number