Description:
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.
Title
- Brief Title: A Phase 1 Dose-Escalation and Cohort-Expansion of VLS-101 in Hematologic Malignancies
- Official Title: A Phase 1 Dose-Escalation and Cohort-Expansion Study of VLS -101 in Subjects With Hematological Malignancies
Clinical Trial IDs
- ORG STUDY ID:
2140-001
- SECONDARY ID:
VLS-101-0001
- NCT ID:
NCT03833180
Conditions
- 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
Interventions
| Drug | Synonyms | Arms |
|---|
| VLS-101 Schedule 1 | | VLS-101 Schedule 1 |
| VLS-101 Schedule 2 | | VLS-101 Schedule 2 |
| VLS-101 Schedule 3 | | VLS-101 Schedule 3 |
Purpose
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.
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| VLS-101 Schedule 1 | Experimental | 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. | |
| VLS-101 Schedule 2 | Experimental | 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. | |
| VLS-101 Schedule 3 | Experimental | 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. | |
Eligibility Criteria
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Maximum tolerated dose (MTD) |
| Time Frame: | 3-4 weeks |
| Safety Issue: | |
| Description: | Recommended starting dose and schedule |
Secondary Outcome Measures
| Measure: | Plasma VLS-101 drug concentrations |
| Time Frame: | Weekly during the first 3-4 weeks and then every 3-4 weeks up to 96 weeks |
| Safety Issue: | |
| Description: | Pharmacokinetics |
| Measure: | 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 |
| Safety Issue: | |
| Description: | Safety |
| Measure: | Serum concentrations of VLS-101-reactive antibodies |
| Time Frame: | Every 3-4 weeks up to 96 weeks |
| Safety Issue: | |
| Description: | Immunogenicity |
| Measure: | 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 |
| Safety Issue: | |
| Description: | Efficacy |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | VelosBio Inc. |
Trial Keywords
- Lymphoma
- Lymphoma, Non-Hodgkin
- Leukemia, B-Cell
- Leukemia, Lymphoid
- Leukemia
- 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
Last Updated
April 2, 2021
