A Study of Zilovertamab Vedotin (MK-2140) as Monotherapy and in Combination in Participants With Aggressive and Indolent B-cell Malignancies (MK-2140-006)

Conditions

• Chronic Lymphocytic Leukemia
• Follicular Lymphoma
• Mantle Cell Lymphoma
• Richter Transformation Lymphoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Zilovertamab vedotin — BIOLOGICAL
  IV infusion
• Nemtabrutinib — DRUG
  Oral tablet

Study Details

The purpose of this study is to assess the safety and tolerability of zilovertamab vedotin as monotherapy and in combination in participants with select B-cell lymphomas including mantle cell lymphoma (MCL), Richter's transformation lymphoma (RTL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL). This study will also evaluate zilovertamab vedotin as monotherapy and in combination with respect to objective response rate. * Cohort A: Participants with relapsed or refractory MCL relapsed or refractory disease after at least 2 prior systemic therapies including a Bruton's tyrosine kinase inhibition/inhibitor (BTKi), and post therapy chimeric antigen receptor T (CAR-T) cell therapy or ineligible for CAR-T cell therapy * Cohort B: Participants with relapsed or refractory RT disease after at least 1 prior systemic therapy * Cohort C: Participants with relapsed or refractory MCL relapsed or refractory disease after at least 1 prior systemic therapy and no prior exposure to a non-covalent BTKi * Cohort D: Participants with relapsed or refractory FL and CLL relapsed or refractory disease after at least 2 prior systemic therapies and have no other available therapy * Cohort E: Participants with relapsed or refractory FL after at least 2 prior systemic therapies and have no other available therapy The primary study hypothesis is that zilovertamab vedotin monotherapy has an increased Objective Response Rate (ORR) per Lugano Response Criteria as assessed by blinded independent central review (BICR). As of Amendment 07, Cohort D is closed to enrollment of participants with CLL and enrollment of participants into Arm 2 (zilovertamab vedotin at Dose 2 on Days 1 \& 8 of each 3 Week Cycle (Q2/3W)). As of Amendment 09, no additional participants with RT will be enrolled in Cohort B; however, those currently enrolled will continue with study intervention treatment (if applicable) until a protocol specified discontinuation criterion is met. Cohort E will be closed, as no participants with FL have been treated in this cohort.

Key Dates

Start date

Jul 21, 2022

Status verified

Jun 2026

Primary completion

May 17, 2029

Completion

May 17, 2029

Study Design

Enrollment

189 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Cohort A, Relapsed or Refractory MCL with 2 Prior Lines of Therapy
  Participants will receive zilovertamab vedotin intravenous (IV) infusion at Dose 1 every 3 weeks (Q3W) until disease progression or discontinuation.
• Experimental: Cohort B, Relapsed or Refractory RT with 1 Prior Line of Therapy
  Participants will receive zilovertamab vedotin IV infusion at Dose 1 every 3 weeks (Q3W) until disease progression or discontinuation.
• Experimental: Cohort C, Relapsed or Refractory MCL with 1 Prior Line of Therapy
  Participants will receive zilovertamab vedotin IV infusion at Dose 2 every 3 weeks (Q3W) combined with nemtabrutinib oral dose daily until disease progression or discontinuation.
• Experimental: Cohort D, Relapsed or Refractory FL and CLL with 2 Prior Lines of Therapy
  Participants will receive either zilovertamab vedotin IV infusion Dose 1 every 3 weeks (Q3W) until disease progression or discontinuation.

Primary Outcome Measure

Percentage of Participants with MCL (Cohort C), FL (Cohort D), and CLL (Cohort D) with ≥1 Adverse Event (AE) [ Time Frame: Up to approximately 81 months ]

Locations (20)

Find similar trials in Anchorage, AK

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