A Study to Evaluate Zilovertamab Vedotin (MK-2140) for Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) (MK-2140-004)

Merck Sharp & Dohme (MSD)

Status and phase: Active, not recruiting; Phase 2

Conditions: Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Treatments: Biological: MK-2140 (zilovertamab vedotin)

Study type: Interventional

Funder types: Industry

Identifiers

NCT05144841

MK-2140-004 (Other Identifier)

2021-003397-32 (EudraCT Number)

2140-004

Details and patient eligibility

About

The purpose of this study is to evaluate zilovertamab vedotin with respect to objective response rate and duration of response per Lugano Response Criteria as assessed by blinded independent central review (BICR). Safety and tolerability will also be evaluated in this Phase 2, single arm, interventional study.

Enrollment: 140 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Has relapsed or refractory (rr) DLBCL; has progressed after at least 2 lines of prior therapy; and has progressed after auto- stem cell transplant (SCT) or are auto-SCT ineligible. Must have received prior multiagent regimen that includes an alkylating agent. anthracycline, and anti-CD20 (cluster of differentiation 20) monoclonal antibody.
• Has histologically confirmed diagnosis of DLBCL.
• Has radiographically measurable DLBCL per the Lugano Response Criteria.
• Should either be post- chimeric antigen receptor T cell therapy (CAR-T) failure or ineligible for CAR-T (for any reason).
• Life expectancy of at least 3 months.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 assessed within 7 days before time of enrollment.
• Has adequate organ function.

Exclusion criteria

• Has received a diagnosis of Primary mediastinal B-cell lymphoma (PMBCL).
• Has undergone solid organ transplant at any time.
• Has a history of any clinically significant cardiovascular conditions within 6 months of screening or serious cardiac arrhythmia requiring medication.
• Has known history of liver cirrhosis.
• Has pericardial effusion or clinically significant 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.
• Transformed DLBCL from indolent lymphoma.
• In participants with prior allo-SCT, acute graft versus host disease (GVHD) or ongoing evidence of chronic GVHD.
• 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 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.
• 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.
• Has an active infection requiring systemic therapy.
• Has a known history of human immunodeficiency virus (HIV) infection.
• Has a known history of hepatitis B or known active hepatitis C virus (HCV).

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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140 participants in 2 patient groups

Arm A

Experimental group

Description:

Participants will receive treatment with zilovertamab vedotin 2.5 mg/kg via intravenous (IV) infusion on Day 1 of each 21-day cycle (every 3 weeks (Q3W)) until documented disease progression or any other discontinuation criterion is met.

Treatment:

Biological: MK-2140 (zilovertamab vedotin)

Biological: MK-2140 (zilovertamab vedotin)

Arm B

Experimental group

Description:

Participants will receive treatment with zilovertamab vedotin 2.25 mg/kg via intravenous (IV) infusion on Day 1 of each 21-day cycle (every 3 weeks (Q3W)) until documented disease progression or any other discontinuation criterion is met.

Treatment:

Biological: MK-2140 (zilovertamab vedotin)

Biological: MK-2140 (zilovertamab vedotin)