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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03833180
Recruitment Status : Recruiting
First Posted : February 6, 2019
Last Update Posted : August 21, 2020
Information provided by (Responsible Party):
VelosBio Inc.

Brief 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.

Condition or disease Intervention/treatment Phase
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 Drug: VLS-101 Schedule 1 Drug: VLS-101 Schedule 2 Drug: VLS-101 Schedule 3 Phase 1

Detailed 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 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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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 210 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Cohorts of 3 to 6 subjects will be sequentially enrolled at progressively higher dose levels within each dose schedule of VLS-101 using a 3+3 dose-escalation design.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Dose-Escalation and Cohort-Expansion Study of VLS -101 in Subjects With Hematological Malignancies
Actual Study Start Date : February 1, 2019
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : June 2021

Arm Intervention/treatment
Experimental: VLS-101 Schedule 1
Open label VLS-101 at 0.5,1.0, 1.5, 2.25, 2.5, 2.75, or 3.0 mg/kg given IV on Day 1 of repeated 21-day cycles.
Drug: VLS-101 Schedule 1
Open-Label VLS-101

Experimental: VLS-101 Schedule 2
Open label VLS-101 at 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, or 2.25 mg/kg given IV on Days 1 and 8 of repeated 21-day cycles.
Drug: VLS-101 Schedule 2
Open-label VLS-101

Experimental: VLS-101 Schedule 3
Open label VLS-101 at 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, or 2.25 mg/kg given IV on Days 1, 8, and 15 of repeated 28-day cycles.
Drug: VLS-101 Schedule 3
Open-label VLS-101

Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) [ Time Frame: 3-4 weeks ]
    Recommended starting dose and schedule

Secondary Outcome Measures :
  1. Plasma VLS-101 drug concentrations [ Time Frame: Weekly during the first 3-4 weeks and then every 3-4 weeks up to 96 weeks ]

  2. Incidence of adverse events and laboratory abnormalities [ Time Frame: Weekly during the first 6-8 weeks and then every 3-4 weeks up to 96 weeks ]

  3. Serum concentrations of VLS-101-reactive antibodies [ Time Frame: Every 3-4 weeks up to 96 weeks ]

  4. Tumor response by published criteria [ Time Frame: Every 8-12 weeks up to 48 weeks and then every 12-18 weeks up to 96 weeks ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03833180

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Contact: Elizabeth M Schmidt 2063005215
Contact: Langdon L Miller, MD 9089066471

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United States, California
City of Hope National Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Andrew Romero    626-256-4673 ext 80478   
UC San Diego Moores Cancer Center Recruiting
La Jolla, California, United States, 92093
Contact: Kimberly Aguilar    858-534-5201   
UCLA Department of Medicine - Hematology/Oncology Recruiting
Los Angeles, California, United States, 90095
Contact: Melinda Catala    310-633-8400 ext 16112   
United States, Nebraska
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198-6840
Contact: Maribeth Hohenstein    402-559-9053   
United States, New York
Northwell Health/CLL Research and Treatment Program Recruiting
New Hyde Park, New York, United States, 11042
Contact: Eunok Kwak, RN    718-470-4046   
Weill Cornell Medical College - New York - Presbyterian Hospital Recruiting
New York, New York, United States, 10065
Contact: Christine Tran    212-746-6738   
University of Rochester Medical Center Recruiting
Rochester, New York, United States, 14642
Contact: Delaney Dretto    585-275-5825   
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Jessica VanLith    503-494-9324   
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Philip Thompson, MD    713-792-7430   
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Maria Badillo, MSN RN OCN    713-745-2714   
United States, Washington
Swedish Cancer Institute Recruiting
Seattle, Washington, United States, 98104
Contact: Ngan Trinh    206-215-2363   
Sponsors and Collaborators
VelosBio Inc.
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Study Director: Langdon L Miller, MD VelosBio Inc.
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Responsible Party: VelosBio Inc. Identifier: NCT03833180    
Other Study ID Numbers: VLS-101-0001
First Posted: February 6, 2019    Key Record Dates
Last Update Posted: August 21, 2020
Last Verified: August 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by VelosBio Inc.:
Lymphoma, Non-Hodgkin
Leukemia, B-Cell
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Follicular
Lymphoma, Mantle-Cell
Burkitt Lymphoma
Lymphoma, Lymphoplasmacytoid
Waldenström Macroglobulinemia
Lymphoma, T-cell
Leukemia, Lymphoid, Acute
Leukemia, Myeloid, Acute
Additional relevant MeSH terms:
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Burkitt Lymphoma
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, T-Cell
Waldenstrom Macroglobulinemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Leukemia, B-Cell
Lymphoma, B-Cell
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders