A Study of VLS-101 in Patients With Solid Tumors

• ClinicalTrials.gov Identifier: NCT04504916
• Recruitment Status: Recruiting
• First Posted: August 7, 2020
• Last Update Posted: December 24, 2020
• Sponsor: VelosBio Inc.
• Information provided by (Responsible Party): VelosBio Inc.

Tracking Information

• First Submitted Date: August 4, 2020
• First Posted Date: August 7, 2020
• Last Update Posted Date: December 24, 2020
• Actual Study Start Date: October 16, 2020
• Estimated Primary Completion Date: July 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 6, 2020)

Change from baseline in tumor dimensions [ Time Frame: Every 9-12 weeks up to 48 weeks and then every 12-18 weeks up to 96 weeks ]

Response

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 6, 2020)

• Safety as assessed by the incidence of adverse events and laboratory abnormalities [ Time Frame: Weekly during the first 3 weeks and then every 3 weeks up to 96 weeks ]
  Safety
• Plasma VLS-101 drug concentrations [ Time Frame: Weekly during the first 3 weeks and then every 3 weeks up to 96 weeks ]
  Pharmacokinetics
• Serum concentrations of VLS-101-reactive antibodies [ Time Frame: Every 3 weeks up to 96 weeks ]
  Immunogenicity

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of VLS-101 in Patients With Solid Tumors
• Official Title: A Phase 2 Study of VLS-101 in Patients With Solid Tumors
• Brief Summary: This is a Phase 2 study evaluating the efficacy, safety, pharmacokinetics, immunogenicity, and pharmacodynamics of VLS-101 in patients with metastatic solid tumors. VLS-101 is an antibody- drug conjugate (ADC) that targets receptor tyrosine kinase-like orphan receptor 1 (ROR1) on cancer cells.

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 enter those cells, where the MMAE is released and can destroy the cancerous cells. In mouse models of human solid tumors, VLS-101 has caused highly significant tumor shrinkage.

This clinical trial is a Phase 2 study evaluating VLS-101 in patients with metastatic solid tumors that are likely to express ROR1. Accrual of subjects with any of the following tumor types is planned:

• Previously treated triple-negative breast cancer (TNBC)
• Previously treated estrogen receptor (ER)-positive, progesterone receptor (PR)-positive, or human epidermal growth factor receptor (HER2)-positive breast cancer
• Previously treated non-squamous, non-small-cell lung cancer (NSCLC) Cohorts of subjects may be added as ROR1 expression information and relevant supporting data becomes available for other tumor types.

VLS-101 is administered intravenously in repeated 3-week cycles with a drug infusion on Day 1 of each cycle. 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 testing is performed to assess for any VLS-101 effects on liver, kidney, and bone marrow (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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Triple-negative Breast Cancer (TNBC)
• Non-squamous Non-small-cell Lung Cancer (NSCLC)
• Estrogen Receptor-positive Breast Cancer
• Progesterone Receptor-positive Breast Cancer
• Human Epidermal Growth Factor 2 Positive Carcinoma of Breast

Intervention

Drug: VLS-101

Open-Label VLS-101

Study Arms

Experimental: VLS-101

Open label VLS-101 at 2.5 mg/kg given IV on Day 1 of repeated 21-day cycles.

Intervention: Drug: VLS-101

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 6, 2020): 90
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2022
• Estimated Primary Completion Date: July 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Men or women of age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Histologically or cytologically confirmed diagnosis of solid tumor as documented in medical records.
• Presence of metastatic disease that has progressed during or following previous treatment appropriate for the disease type.
• Presence of radiographically measurable disease.
• Availability of pretreatment tumor tissue.
• Adequate hematological profile
• Adequate hepatic profile
• Adequate renal function
• Negative testing or adequate therapy 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:

• Peripheral neuropathy of Grade >1.
• Presence of malignancy involving the central nervous system.
• Presence of another major cancer.
• Uncontrolled ongoing infection.
• Significant cardiovascular disease or electrocardiogram (ECG) abnormalities.
• Known diagnosis of liver cirrhosis.
• Pregnancy or breastfeeding.
• Major surgery within 4 weeks before the start of study therapy.
• Prior treatment with a ROR-1-directed therapy.
• Known tumor resistance or intolerance to a prior MMAE-containing drug.
• 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Anthony Viggiano; 2062270171; aviggiano@velosbio.com

Contact: Elizabeth Schmidt; 2063005215; lschmidt@velosbio.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04504916
• Other Study ID Numbers: VLS-101-0003
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: VelosBio Inc.
• Study Sponsor: VelosBio Inc.
• Collaborators: Not Provided

Investigators

• Study Director: Langdon L Miller, MD; VelosBio Inc.

• PRS Account: VelosBio Inc.
• Verification Date: December 2020