A Study of Zilovertamab Vedotin (MK-2140) in Combination With Standard of Care in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (rrDLBCL) (MK-2140-003)

Conditions

• DLBCL
• Diffuse Large B-Cell Lymphoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Zilovertamab vedotin — BIOLOGICAL
  Intravenous (IV) Infusion 1.5 mg/kg, 1.75 mg/kg, 2.0 mg/kg, 2.25 mg/kg, 2.5 mg/kg
• Rituximab — BIOLOGICAL
  IV Infusion 375 mg/m\^2
• Gemcitabine — DRUG
  IV Infusion 1000 mg/m\^2
• Oxaliplatin — DRUG
  IV Infusion 100 mg/m\^2
• Bendamustine — DRUG
  IV Infusion 90 mg/m\^2
• Granulocyte Colony-Stimulating Factor (G-CSF) — DRUG
  Prophylactic G-CSF will be administered at each cycle of zilovertamab vedotin as per the institutional guidelines.

Study Details

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.

Key Dates

Start date

Jan 14, 2022

Status verified

Jun 2026

Primary completion

Sep 24, 2027

Completion

Sep 24, 2027

Study Design

Enrollment

290 participants (estimated)

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: ZV + R-GemOx (Part 1)
  Participants in this arm will receive doses of ZV (from 1.5 mg/Kg up to 2.5 mg/Kg) plus Rituximab 375 mg/m\^2, Gemcitabine 1000 mg/m\^2 and Oxaliplatin 100 mg/m\^2 (R-GemOx) given intravenously on Day 1 of repeated 21-day cycles. Treatment will continue for up to 6 cycles.
• Experimental: ZV + R-GemOx (Part 2)
  Using the recommended Phase 2 dose (RP2D) dose of ZV plus R-GemOx from Part 1, participants will receive ZV plus R-GemOx given intravenously on Day 1 of repeated 21-day cycles. Treatment will continue for up to 6 cycles or until progressive disease or discontinuation.
• Active Comparator: R-GemOx (active control for Part 2)
  Participants will receive R-GemOx given intravenously on Day 1 of repeated 21-day cycles. Treatment will continue for up to 6 cycles or until progressive disease or discontinuation.
• Experimental: ZV + BR (Part 2)
  Using RP2D from Part 1, participants will receive ZV plus Rituximab 375 mg/m\^2, given intravenously on Day 1 and Bendamustine 90 mg/m\^2 given intravenously on Day 1 and 2, of repeated 21-day cycles. Treatment will continue for up to 6 cycles or until progressive disease or discontinuation.
• Active Comparator: Bendamustine Rituximab (BR)
  Participants will receive Rituximab 375 mg/m\^2, given intravenously on Day 1 Bendamustine 90 mg/m\^2 given intravenously on Day 1 and 2 of repeated 21-day cycles. Treatment will continue for up to 6 cycles or until progressive disease or discontinuation.
• Experimental: ZV + BR (Part 1)
  Participants in this arm will receive doses of ZV (from 1.5 mg/Kg up to 2.5 mg/Kg) plus Rituximab 375 mg/m\^2, Bendamustine 90 mg/m\^2 (BR) given intravenously on Day 1 and 2 of repeated 21-day cycles. Treatment will continue for up to 6 cycles.

Primary Outcome Measure

Number of participants who experienced dose-limiting toxicities (DLTs) in Part 1 [ Time Frame: Up to ~6 weeks ]

Central Contacts

• Toll Free Number
  1-888-577-8839
  [email protected]

Locations (26)

Find similar trials in Glendale, AZ

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