A Study of Zilovertamab Vedotin (MK-2140) (VLS-101) in Participants With Hematologic Malignancies (MK-2140-001)

A Phase 1 Dose-Escalation and Cohort-Expansion Study of VLS-101 in Subjects With Hematological Malignancies (waveLINE-001)

The purpose of this study is to evaluate the safety, pharmacokinetics, immunogenicity, and efficacy of zilovertamab vedotin given intravenously (IV) across a range of dose levels in participants with previously treated hematological cancers including acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), Burkitt lymphoma (BL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), Richter transformation lymphoma (RTL), and T-cell non-Hodgkin lymphoma (NHL).

Inclusion Criteria:

• Men or women of age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Histological diagnosis of CLL/SLL, MCL, FL, MZL, DLBCL, RTL, BL, LPL/WM, T-cell NHL, ALL, or AML as documented in medical records.
• Hematological cancer under study has been previously treated and has progressed during or relapsed after prior systemic therapy.
• Hematological cancer is unlikely to be responsive to established therapies known to provide clinical benefit or the study candidate has developed an intolerance to established therapies known to provide clinical benefit.
• Presence of measurable cancer including CLL/SLL, MCL, FL, MZL, DLBCL, RTL, BL, LPL/WM, T-cell NHL, ALL, and AML.
• Current medical need for therapy due to disease-related symptoms or complications, cytopenias, lymphadenopathy, organomegaly, extranodal organ involvement, or progressive disease.
• Availability of pretreatment tumor tissue.
• Completion of all previous therapy (including surgery, radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of cancer ≥1 week before the start of study therapy.
• All acute toxic effects of any prior antitumor therapy (not including hydroxyurea, cytarabine, and/or cyclophosphamide used in subjects with acute leukemia) resolved to ≤Grade 1 before the start of study therapy (with the exception of alopecia [Grade 1 or 2 permitted] or selected laboratory parameters [Grade 1 or Grade 2 permitted with exceptions.
• Adequate bone marrow function.
• Adequate hepatic profile.
• Adequate renal function.
• Adequate coagulation profile.
• Negative antiviral serology.
• For female participants of childbearing potential, a negative serum pregnancy test.
• For both male and female participants, willingness to use protocol-recommended method of contraception from the start of the screening period until ≥6 months after the final dose of study therapy.
• Willingness and ability of the participant to comply with study activities.
• Evidence of a personally signed informed consent document.
• Previous treatment with an MMAE-containing drug is allowed.

Exclusion Criteria:

• Presence of malignancy involving the central nervous system.
• Presence of another cancer with disease manifestations or therapy that could adversely affect participant safety or longevity, create the potential for drug-drug interactions, or compromise the interpretation of study results.
• Significant cardiovascular disease within 3 months prior to start of study therapy.
• Significant screening electrocardiogram (ECG) abnormalities.
• Uncontrolled ongoing systemic bacterial, fungal, or viral infection.
• Known diagnosis of liver cirrhosis.
• Pregnancy or breastfeeding.
• Candidacy for hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor (CAR)-T-cell therapy with access to HSCT or CAR-T cells and a willingness to undergo such therapy.
• In participants with prior HSCT, evidence of graft-versus-host disease (GVHD) with Grade ≥2 serum bilirubin, Grade ≥3 skin involvement, or Grade ≥3 diarrhea.
• Prior solid organ transplantation.
• Major surgery within 4 weeks before the start of study therapy.
• Prior therapy with a receptor tyrosine kinase-like orphan receptor 1 (ROR1)-directed therapy.
• Has ongoing corticosteroid therapy (exceeding 30 mg daily of prednisone equivalent). Prednisone equivalent dosing must have been stable for at least 4 weeks prior to Cycle 1 Day 1 (C1D1). If corticosteroid treatment is required for lymphoma symptom control prior to C1D1, up to 100 mg per day of prednisone equivalent can be given for up to 5 days. In that case, all tumor assessments must have been completed prior to the start of corticosteroid treatment.
• Use of a strong inhibitor or inducer of cytochrome P450 (CYP) 3A4.
• Use within 7 days prior to the start of study therapy of a drug known to prolong the QT interval.
• Concurrent participation in another therapeutic or imaging clinical trial.
• Presence of a medical condition that (in the judgement of the investigator) interferes with the ability of the participant to participate in the study.
• Has baseline peripheral neuropathy >Grade 1.