This is a Phase 1 first in human, open label, multi-center, dose escalation study to evaluate the safety, tolerability, PK, anti-tumor activity and pharmacodynamic effects of SL-172154 in subjects with ovarian cancer.
This Phase 1 trial will evaluate the safety, tolerability, pharmacokinetics, anti-tumor and pharmacodynamic effects of SL-172154 and identify the dose and schedule i.e., recommended Phase 2 dose for future development (RP2D). Subjects eligible for enrollment are required to have platinum-ineligible ovarian, fallopian tube, and primary peritoneal cancers. The study design consists of dose escalation cohorts, an optional pharmacodynamic cohort, and an optional dose expansion cohort. In the dose escalation phase of the study, subjects will be enrolled into sequential dose levels. The study may also enroll a pharmacodynamic cohort to obtain additional pharmacodynamic data at one or more dose levels that have completed evaluation for safety without exceeding the maximum tolerated dose (MTD). Subjects enrolled in the pharmacodynamic cohort will not inform dose escalation decisions. A dose expansion cohort may be opened to further characterize safety, tolerability, PK, anti-tumor activity, and pharmacodynamic data to inform the selection of a RP2D.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
27
The investigational product (IP), SL-172154, is a novel fusion protein consisting of human SIRPα and CD40L (SIRPα -Fc-CD40L) linked via a human Fc.
City of Hope
Duarte, California, United States
START Midwest
Grand Rapids, Michigan, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
Stephenson Cancer Center at Oklahoma University
Oklahoma City, Oklahoma, United States
Safety Profile of SL-172154
Number of participants with treatment emergent adverse events
Time frame: From Day 1 to 90 days after Last Dose of SL-172154
Maximum Tolerated Dose (MTD) of SL-172154
Number of participants with dose limiting toxicities (DLTs)
Time frame: From Day 1 to 90 days after Last Dose of SL-172154
Recommended Phase 2 Dose (RP2D) for SL-172154
Based on review of all data, including safety, tolerability, PK, antitumor activity, and PD effects
Time frame: Approximately 24 months
Assess Preliminary Evidence of Anti-tumor Activity of SL-172154
Number of participants with an objective response per investigator assessment according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1). Objective response includes complete response (disappearance of all target lesions) and partial response (\>/= 30% decrease in the sum of the longest diameter of target lesions).
Time frame: Approximately 24 months
Immunogenicity to SL-172154
Number of participants with positive anti-drug antibody (ADA) titer, sustained ADA response (positive ADA in \>/= 2 samples without reverting to negative ADA or positive ADA in the last sample), or persistent ADA response (positive ADA in \>/= 2 samples where the first and last samples are \>/= 16 weeks apart, or positive ADA in the last sample, or only one sample but \< 16 weeks before a negative last sample).
Time frame: Approximately 24 months
Maximum Serum Concentration (Cmax) of SL-172154
The Cmax is the maximum observed serum concentration of SL-172154 following single and multiple doses
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Sarah Cannon Research Institute
Nashville, Tennessee, United States
START Mountain Region
West Valley City, Utah, United States
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle = 28 days)
Minimum Serum Concentration (Cmin) of SL-172154
The Cmin is the minimum observed serum concentration of SL-172154 following at least one dose
Time frame: Cycle 1 Day 15 and Cycle 2 Day 1 (each cycle = 28 days)
Time at Which Maximum Concentration of SL-172154 is Observed (Tmax)
The Tmax is the time at which the maximum concentration of SL-172154 is observed following single and multiple doses
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle = 28 days)
Area Under the Serum Concentration-time Curve (AUC)
The AUC is the area under the serum concentration time curve following single and multiple doses of SL-172154. AUC (0-last; from time 0 to the last quantifiable concentration) is reported for C1D1 and AUC (tau; over a dosing interval) is reported for C1D15 and C2D1.
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle = 28 days)
Terminal Elimination Half-life (t1/2)
Terminal elimination half-life (t1/2) of SL-172154
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle = 28 days)
Clearance (CL)
Clearance of SL-172154
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle = 28 days)
Volume of Distribution
Volume of distribution of SL-172154
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle = 28 days)