A Phase 1 Dose-Escalation and Cohort-Expansion of VLS-101 in Hematologic Malignancies

Summary

Participation Requirements

Description

ROR1 is a cell-surface protein that has an important role in the formation of the nervous systems, bones, and blood vessels during the early development of the embryo. ROR1 disappears by the time of birth and is not detected on normal human tissues in childhood or adulthood. However, ROR1 can reappe...

ROR1 is a cell-surface protein that has an important role in the formation of the nervous systems, bones, and blood vessels during the early development of the embryo. ROR1 disappears by the time of birth and is not detected on normal human tissues in childhood or adulthood. However, ROR1 can reappear on malignant tissues, including on hematologic cancers. This selective expression of ROR1 on cancerous cells but not on normal cells offers the potential for using VLS 101 to specifically kill the cancer cells while sparing normal cells. VLS-101 is an investigational drug consisting of a monoclonal antibody that binds to ROR1 coupled with a potent toxin called monomethyl auristatin E (MMAE). After the antibody binds to ROR1 on cancer cells, the ADC can internalize into those cells, where the MMAE is released and can destroy the malignant cells. In mouse models of human hematologic cancers, VLS-101 has caused highly significant tumor shrinkage. This clinical trial is a Phase 1 study evaluating VLS-101 across a range of dose levels. People with several types of hematological cancers are eligible, including those with previously treated 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), or T-cell lymphoma. VLS-101 is administered intravenously in repeated 3-week cycles with a drug infusion on Day 1 of each cycle (Schedule 1); in repeated 3-week cycles with drug infusions on Days 1 and 8 of each cycle (Schedule 2); or in repeated 4-week cycles with drug infusions on Days 1, 8, and 15 of each cycle (Schedule 3). The primary goal of this study is to define a maximum tolerated dose (MTD) for each schedule of administration. For each patient, therapy can continue as long as the patient is tolerating the therapy and appears to have evidence of benefit. During the study, blood and electrocardiogram testing is performed to assess for any VLS-101 effects on liver, kidney, bone marrow, and heart function (safety); evaluate how much VLS 101 and its breakdown products appear in the blood (pharmacokinetics); determine if VLS 101 is altering cancer cells or cancer-related proteins (pharmacodynamics); measure for antidrug antibodies to VLS 101 (immunogenicity); and examine tumors to understand whether the types of cancer cells will affect the study drug effects. Scans are performed periodically to assess for changes in tumor status.

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