Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at La Jolla, California and other locations
Dates
study started
estimated completion

Description

Summary

This is a Phase 1 study evaluating the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and efficacy of VLS-101, an antibody-drug conjugate (ADC) that targets receptor tyrosine kinase-like orphan receptor 1 (ROR1) on cancer cells. The study is evaluating VLS-101 in patients with previously treated hematological cancers.

Official Title

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

Details

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.

Keywords

Chronic Lymphocytic Leukemia Mantle Cell Lymphoma Follicular Lymphoma Marginal Zone Lymphoma Diffuse Large B-cell Lymphoma Richter Transformation Lymphoma Burkitt Lymphoma Lymphoplasmacytoid Lymphoma T-cell Non-Hodgkin Lymphoma Acute Lymphoid Leukemia Acute Myeloid Leukemia Waldenstrom Macroglobulinemia Lymphoma Lymphoma, Non-Hodgkin Leukemia, B-Cell Leukemia, Lymphoid Leukemia Leukemia, Lymphocytic, Chronic, B-Cell Lymphoma, Follicular Lymphoma, Mantle-Cell Lymphoma, Lymphoplasmacytoid Waldenström Macroglobulinemia Lymphoma, T-cell Leukemia, Lymphoid, Acute Leukemia, Myeloid, Acute Lymphoma, Large B-Cell, Diffuse Precursor Cell Lymphoblastic Leukemia-Lymphoma VLS-101 Schedule 1 VLS-101 Schedule 2 VLS-101 Schedule 3

Eligibility

For people ages 18 years and up

Inclusion:

  • Men or women of age ≥18 years.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
  • Presence of measurable B-cell cancer that has progressed during or relapsed after prior systemic therapy.
  • Availability of pretreatment tumor tissue.
  • All acute toxic effects of prior antitumor therapy resolved to Grade ≤1
  • Adequate bone marrow function
  • Adequate hepatic profile
  • Adequate renal function
  • Adequate coagulation profile
  • Negative testing for human immunodeficiency virus (HIV), hepatitis B, and hepatitis C
  • For female subjects of childbearing potential, a negative serum pregnancy test.
  • For both male and female subjects, willingness to use adequate contraception
  • Willingness and ability of the subject to comply with study activities.
  • Evidence of a personally signed informed consent document.

Exclusion Criteria:

  • Presence of malignancy involving the central nervous system.
  • Presence of another major cancer.
  • Significant cardiovascular disease or electrocardiogram (ECG) abnormalities.
  • Uncontrolled ongoing infection.
  • Pregnancy or breastfeeding.
  • Candidacy for hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor (CAR)-T-cell therapy (based on investigator judgment).
  • 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 certain excluded drugs.
  • Ongoing immunosuppressive therapy other than corticosteroids.
  • Use of a strong inhibitor or inducer of cytochrome P450 (CYP) 3A4.
  • Use 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 subject to participate in the study.

Locations

  • UC San Diego Moores Cancer Center accepting new patients
    La Jolla California 92093 United States
  • UCLA Department of Medicine - Hematology/Oncology accepting new patients
    Los Angeles California 90095 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
VelosBio Inc.
ID
NCT03833180
Phase
Phase 1
Study Type
Interventional
Last Updated