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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
250
SLV-154
Hoag Memorial Hospital Presbyterian
Newport Beach, California, United States
RECRUITINGWashington University
St Louis, Missouri, United States
Phase 1a: MTD and/or RDR
Determination of the MTD (maximum tolerated dose) and/or RDR (recommended dosing regimen) for SLV-154.
Time frame: Through the duration of treatment, up to approximately 18 months
Phase 1b: Objective response rate (ORR)
ORR assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria and defined as the percentage of participants with confirmed complete response (CR) or confirmed partial response (PR).
Time frame: Through the duration of treatment, up to approximately 18 months
SLV-154 administration
SLV-154 drug administration as assessed by prescribing records
Time frame: Through the duration of treatment, up to approximately 18 months
SLV-154 Safety
Collection of type, frequency, severity, timing of onset, duration, and relationship to study drug of any treatment-emergent adverse events (TEAEs); laboratory abnormalities; vital sign/oxygen saturation abnormalities; adverse electrocardiogram (ECG) findings; DLTs; serious adverse events (SAEs); adverse events of special interest (AESIs); or adverse events (AEs) leading to interruption, modification, or discontinuation of study drug administration.
Time frame: Through the duration of treatment, up to approximately 18 months
Evaluation of use of concomitant medications
Type, frequency, and timing of use of supportive care and other concomitant medications
Time frame: Through the duration of treatment, up to approximately 18 months
SLV-154 Pharmacokinetics
Evaluation of the pharmacokinetic profile of SLV-154
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Astera Cancer Care
East Brunswick, New Jersey, United States
RECRUITINGMemorial Sloan Kettering Cancer Center
New York, New York, United States
RECRUITINGUniversity Hospitals Cleveland Medical Center
Cleveland, Ohio, United States
RECRUITINGThe James Outpatient Care West Center
Columbus, Ohio, United States
RECRUITINGFox Chase Cancer Center
Philadelphia, Pennsylvania, United States
RECRUITINGMD Anderson Cancer Center
Houston, Texas, United States
RECRUITINGOncology Consultants
Houston, Texas, United States
RECRUITINGMays Cancer Center; University of Texas Health San Antonio
San Antonio, Texas, United States
RECRUITING...and 2 more locations
Time frame: Varying timepoints through the duration of treatment, up to approximately 18 months
Immunogenicity
Measurement of changes in titers of circulating SLV 154-reactive antibodies (as assessed using immunoassay methods)
Time frame: Varying timepoints through the duration of treatment, up to approximately 18 months
Time to Response (TTR)
TTR: interval from the start of study drug administration to the first documentation of objective tumor regression
Time frame: Up to approximately 36 months
Duration of Response (DOR)
DOR: interval from the first documentation of objective tumor regression to the earlier of the first documentation of disease progression or death from any cause
Time frame: Up to approximately 36 months
4-month progression-free survival (PFS4)
PFS4: proportion of subjects who are alive and have not experienced disease progression at 4 months after the start of study drug administration
Time frame: Up to approximately 36 months
6-month progression-free survival (PFS6)
PFS6: proportion of subjects who are alive and have not experienced disease progression at 6 months after the start of study drug administration
Time frame: Up to approximately 36 months
Time to treatment failure (TTF)
TTF: interval from the start of study drug administration to the earliest of the first documentation of disease progression, the permanent cessation of study drug due to an AE, or death from any cause
Time frame: Up to approximately 36 months
Overall survival (OS)
OS: interval from the start of study drug administration to death from any cause
Time frame: Up to approximately 36 months
Disease benefit ratio (DBR)
DBR: proportion of subjects who experience CR, PR, or stable disease with tumor reduction (SDTR)
Time frame: Up to approximately 36 months
Progression free survival (PFS)
PFS: interval from the start of study drug administration to the earlier of the first documentation of disease progression or death from any cause
Time frame: Up to approximately 36 months
Duration of disease benefit (DDB)
DDB: interval from the first documentation of objective tumor regression to the earlier of the first documentation of disease progression or death from any cause in subjects with disease benefit
Time frame: Up to approximately 36 months
Percent change in tumor dimensions
percent change from baseline in the sum of the longest diameters of non-nodal target lesions and the shortest diameters of nodal target lesions
Time frame: Up to approximately 36 months