SLV-154 Treatment of Advanced Cancers

A Phase 1 Dose-Escalation/Expansion Study of SLV-154 in Subjects With Advanced Cancers

This is a Phase 1 study comprising a Phase 1a dose-escalation portion and a Phase 1b expansion portion evaluating the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and efficacy of SLV-154 across a range of dose levels when administered to subjects with advanced solid tumors.

A Bayesian optimal interval (BOIN) design with a target dose-limiting toxicity (DLT) rate for the maximum tolerated dose (MTD) of 27% and an estimated maximum sample size of ~70 subjects will be used to guide the dose escalation and determine the recommended dosing regimen (RDR) of SLV-154. Once the initial RDR is established in the Phase 1a portion of this study, further development in the Phase 1b expansion portion of this study will be considered in patients with specific cancers. In the Phase 1b part of this study, enrollment of each tumor-specific cohort will be performed using a Simon 2-stage optimal design.

SLV-154 will be administered intravenously (IV) in repeated 3-week cycles. Treatment will continue until progressive disease or discontinuation.

Inclusion Criteria:

1. Men or women (as appropriate for cancer type) of age ≥12 years.
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
3. Histologically or cytologically confirmed diagnosis of advanced cancer as documented in medical records.
4. Presence of metastatic or recurrent locally advanced cancer.
5. Presence of radiographically measurable disease.
6. Prior receipt of one or more commercially available therapies that are indicated within product labelling or recommended under current guidelines as appropriate treatment for the subject's cancer (unless evolving data support application of SLV-154 in previously untreated subjects with high unmet medical need and inadequate and/or poorly tolerated treatment options).
7. Availability of tumor tissue from a fresh tumor biopsy obtained by a core needle, excisional, or incisional biopsy; or punch biopsy (for cutaneous disease); or archival tumor sample from a previous biopsy.
8. Availability of computed tomography (CT) or magnetic resonance imaging (MRI) of chest, abdomen, and pelvis, and/or fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT (if appropriate for tumor type) (with PET from base of the skull to mid-thigh, if performed) within 35 days before study drug administration.
9. Completion of all previous therapy (including surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, or investigational therapy) for the treatment of cancer ≥1 week before the start of study drug administration.
10. Adequate hematological profile.
11. Adequate coagulation profile.
12. Adequate hepatic profile.
13. Adequate renal function.
14. Negative viral serology or adequate therapy for human immunodeficiency virus (HIV), hepatitis B (HBV), and hepatitis C (HCV) infection.
15. For female subjects of childbearing potential, a negative serum pregnancy test.
16. For female subjects of childbearing potential, willingness to use a protocol-recommended method of contraception from the start of the screening period until ≥6 months after the final dose of study therapy.
17. For male subjects who can father a child and are having intercourse with females of childbearing potential who are not using adequate contraception, willingness to use a protocol-recommended method of contraception from the start of study therapy until ≥6 months after the final dose of study therapy and to refrain from sperm donation from the start of study therapy until ≥12 months after administration of the final dose of study therapy.
18. Willingness and ability of the subject to comply with scheduled visits, the drug administration plan, protocol-specified laboratory tests, other study procedures (including required tumor biopsy/aspirations and/or radiographic studies), and study restrictions.
19. Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation.

Exclusion Criteria:

1. Unstable malignancy involving the central nervous system.
2. Presence of another cancer with disease manifestations or therapy that could adversely affect subject safety or longevity, create the potential for drug-drug interactions, or compromise the interpretation of study results.
3. Uncontrolled ongoing systemic bacterial, fungal, or viral infection (including upper respiratory tract infection) at the time of start of study therapy.
4. Significant cardiovascular event or comorbidity.
5. Significant screening ECG abnormalities.
6. Pregnancy or breastfeeding.
7. Major surgery within 3 weeks before the start of study therapy.
8. Use of a strong inhibitor or inducer of CYP3A4 or CYP1A2.
9. Concurrent participation in another therapeutic or imaging clinical trial.
10. Other conditions likely to interfere with a subject's ability to participate in the study.