A Study of VLS-101 in Patients With Solid Tumors
A Study of VLS-101 in Patients With Solid Tumors
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.
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.
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.