This is a Phase 1 dose-escalation study evaluating the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and efficacy of SLV-324 across a range of dose levels when administered to subjects with metastatic 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-324. SLV-324 will be administered intravenously (IV) in repeated cycles. Treatment will continue until progressive disease or discontinuation.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
70
SLV-324 will be administered as an IV infusion
Hoag Memorial Hospital Presbyterian
Newport Beach, California, United States
RECRUITINGWashington University
St Louis, Missouri, United States
RECRUITINGUniversity Hospitals Cleveland Medical Center
Cleveland, Ohio, United States
MTD or RDR
Determination of the MTD (maximum tolerated dose) and/or RDR (recommended dosing regimen) for SLV-324
Time frame: Through the duration of treatment, up to approximately 18 months
SLV-324 Administration as Assessed by Prescribing Records
Number of infusions prescribed and administered, body-weight-adjusted and total doses administered, duration of infusions, and number of infusion delays or interruptionsSLV-324 administration as assessed by prescribing records
Time frame: Through the duration of treatment, up to approximately 18 months
SLV-324 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 (dose-limiting toxicities), serious adverse events (SAEs), or adverse events (AEs) leading to interruption, modification, or discontinuation of study drug administration.
Time frame: Up to approximately 18 months.
Evaluation of use of supportive care and other 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-324 Pharmacokinetics: Maximum Concentration (Cmax)
Cmax of SLV-324 antibody-drug conjugate, total antibody, and free payload
Time frame: Varying timepoints through the duration of treatment, up to approximately 18 months
Immunogenicity
Measurement of changes in titers of circulating SLV-324-reactive antibodies (as assessed using immunoassay methods)
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Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
RECRUITINGMD Anderson Cancer Center
Houston, Texas, United States
RECRUITINGMays Cancer Center; University of Texas Health San Antonio
Houston, Texas, United States
RECRUITINGUniversity of Washington / Fred Hutchinson Cancer Center
Seattle, Washington, United States
RECRUITINGTime frame: Varying timepoints through the duration of treatment, up to approximately 18 months
Objective Response Rate (ORR)
ORR assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 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
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.
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
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
SLV-324 Pharmacokinetics: Time to Maximum Concentration (Tmax)
Tmax of SLV-324 antibody-drug conjugate, total antibody, and free payload
Time frame: Varying timepoints through the duration of treatment, up to approximately 18 months
SLV-324 Pharmacokinetics: Area Under the Curve (AUC)
AUC of SLV-324 antibody-drug conjugate, total antibody, and free payload
Time frame: Varying timepoints through the duration of treatment, up to approximately 18 months
SLV-324 Pharmacokinetics: half-life ( t1/2)
t1/2 of SLV-324 antibody-drug conjugate, total antibody, and free payload
Time frame: Varying timepoints through the duration of treatment, up to approximately 18 months