FDA Grants Fast Track and Orphan Drug Designations to VLS-101 for Treatment of MCL


The FDA granted a Fast Track and Orphan Drug designation to VLS-101 for the treatment of patients with mantle cell lymphoma.

The FDA has granted a Fast Track and Orphan Drug designation to VLS-101, a novel first-in-class antibody-drug conjugate targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1), for the treatment of patients with mantle cell lymphoma, announced VelosBio Inc. in a press release.

“We are pleased to receive FDA Fast Track and Orphan Drug designation for VLS-101 in mantle cell lymphoma, which is a significant milestone for VelosBio as we continue to advance our pipeline of ROR1-directed therapeutics,” said Dave Johnson, chief executive officer, VelosBio, in a statement. “We look forward to working closely with the FDA to advance our investigational therapeutic and believe VLS-101 could be an important new treatment option for patients with mantle cell lymphoma.”

The company is currently enrolling patients to a phase 1 dose-escalation and cohort-expansion clinical trial (NCT03833180), which is evaluating VLS-101 as treatment of patients with hematologic malignancies, including mantle cell lymphoma. The study aims to evaluate several dose levels of this agent in patients with mantle cell, as well as those with acute lymphocytic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia/small lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma, among other hematologic malignancies.

The drug is administered intravenously in continuous 3-week cycles, in which a drug infusion takes place on day 1 of each cycle in the first schedule, on days 1 and 8 of each 3-week cycle in the second schedule, and on days 1, 8, and 15 in every cycle of a repeated 4-week cycle. The primary end point of the study is to determine the maximum tolerated dose for each schedule of administration. Therapy may be continued as long as the patient has evidence of benefit and appears to be tolerated the drug.

Patients will be monitoring via blood and electrocardiogram testing to assess for any potential effects of VLS-101 on the liver, kidney, bone marrow, and heart function. The study investigators will also evaluate how much of the drug and its breakdown products appear in the blood and determine if the drug is altering cancer cells or cancer-related proteins. They will also measure for anti-drug antibodies to the treatment and whether the types of cancer cells will impact the effects of VLS-101.

On the first schedule, the dosing of VLS-101 will begin at 0.5 mg/kg and end at 3.0 mg/kg, whereas the other 2 schedules will range from 0.75 to 2.25 mg/kg. Each cohort is expected to enroll 3 to 6 patients.

Secondary end points of the study include plasma VLS-101 concentrations, incidence of adverse events and laboratory abnormalities, serum concentrations of VLS-101 antibodies, and tumor response.

To be included in the study, patients must be over the age of 18 years and have an ECOG performance status of 0 to 2. Patients must also have measurable B-cell cancer that has progressed during or relapsed after a prior systemic therapy, available pretreatment tumor tissue, and resolution of all acute toxic effects from prior antitumor therapy to grade ≤1. Patients are ineligible for the study if they have a malignancy involving the central nervous system, another major cancer, or significant cardiovascular disease or electrocardiogram abnormalities.

The study is being conducted at several locations across the United States.

VLS-101 binds to ROR1 expressed on tumor cells, which results in internalization of the antibody-drug conjugate-ROR1 complex. Within the tumor cells, the lysosomal enzymes release monomethyl auristatin, an anti-microtubule cytotoxin, which will allow for a disruption in the microtubule network within the cell, ultimately inducing subsequent cell-cycle arrest and apoptotic tumor cell death.

The agent has demonstrated activity in vivo, which included complete regression of tumors in nonclinical models of both hematologic malignancies and solid tumors.

Mantle cell lymphoma, which is an aggressive and rare form of non-Hodgkin lymphoma, is more common among male patients compared with females. It commonly appears in patients who are over the age of 60 and is usually widespread to the lymph nodes, bone marrow, and spleen by diagnosis.

The Fast Track designation will help expedite the review process for VLS-101 to treat and fulfill an unmet medical need, while the Orphan Drug designation will also support the development of this agent as potential treatment for an underserved patient population. If relevant criteria are met, a Priority Review may be designated for VLS-101 as well.


VelosBio announces FDA fast track and orphan drug designations for VLS-101 in patients with mantle cell lymphoma. News Release. VelosBio Inc. August 31, 2020. Accessed August 31, 2020. https://bit.ly/2YPOg8m

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