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

This is a Phase 1 dose-escalation study evaluating the safety, pharmacokinetics,
pharmacodynamics, immunogenicity, and efficacy of the novel drug, VLS-101, across a range of
dose levels when administered to subjects with previously treated relapsed or refractory
chronic lymphocytic leukemia/small lymphocytic lymphoma, mantle cell lymphoma, follicular
lymphoma, marginal zone lymphoma, diffuse large B-cell lymphoma, or Richter transformation
lymphoma.

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.