A Phase 1a/1b Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PY159 as a Single Agent and In Combination with Pembrolizumab in Subjects with Advanced Solid Tumors
Name: PY159 Single agent dose level 1
Name: PY159 Single agent dose level 2
Name: PY159 Single agent dose level 3
Name: PY159 Single agent dose level 4
Name: PY159 Single agent dose level 5
Name: PY159 Single agent dose level 6
Name: PY159 Single agent dose level 7
Name: PY159/Pembrolizumab Combination dose level 1
Name: PY159/Pembrolizumab Combination dose level 2
Name: PY159/Pembrolizumab Combination dose level 3
Name: PY159/Pembrolizumab Combination dose level 4
Name: PY159 Single agent dose expansion cohort 1
Name: PY159 Single agent dose expansion cohort 2
Name: PY159/Pembrolizumab Combination dose expansion cohort 1
Name: PY159/Pembrolizumab Combination dose expansion cohort 2
Name: PY159/Pembrolizumab Combination dose expansion cohort 3
Name: PY159/Pembrolizumab Combination dose expansion cohort 4
Description: Adverse Events will be summarized by MedDRA system organ class and preferred term. Separate tabulations will be produced for all treatment emergent AEs, treatment related AEs, Serious Adverse Events (SAEs), discontinuations due to AEs, and AEs of at least NCI CTCAE grade 3 severity.
Measure: Incidence of Adverse Events (AE) Time: 12 monthsDescription: Measure PY159 concentration at the end of infusion (CEOI) after the first dose.
Measure: Measure PY159 concentration at the end of infusion (CEOI) Time: 12 monthsDescription: Measure PY159 maximum concentration (Cmax) at various time points during Cycle 1. All subjects who received at least 1 dose of PY159 and have at least 1 measured concentration at a scheduled PK time point after start of dosing.
Measure: Measure PY159 maximum concentration (Cmax) Time: 12 monthsDescription: Measure PY159 concentration at the trough level (Ctrough). All subjects who received at least 1 dose of PY159 and have at least 1 measured concentration at a scheduled PK time point after start of dosing.
Measure: Measure PY159 concentration at the trough level (Ctrough) Time: 12 monthsDescription: Determining PY159 time to maximum concentration (Tmax) during Cycle 1.
Measure: Determining PY159 time to maximum concentration (Tmax) Time: 12 monthsDescription: Measure PY159 Area under the curve (AUC)0-t. All subjects who received at least 1 dose of PY159 and have at least 1 measured concentration at a scheduled PK time point after start of dosing for at least 1 PK analyte.
Measure: Measure PY159 Area under the curve (AUC)0-t Time: 12 monthsDescription: Measure PY159 half-life (T1/2). All subjects who received at least 1 dose of PY159 and have at least 1 measured concentration at a scheduled PK time point after start of dosing for at least 1 PK analyte.
Measure: Measure PY159 half-life (T1/2) Time: 12 monthsDescription: Measure PY159 Clearance (CL). All subjects who received at least 1 dose of PY159 and have at least 1 measured concentration at a scheduled PK time point after start of dosing for at least 1 PK analyte.
Measure: Measure PY159 Clearance (CL) Time: 12 monthsDescription: Measure PY159 Volume at Steady State (Vss). All subjects who received at least 1 dose of PY159 and have at least 1 measured concentration at a scheduled PK time point after start of dosing for at least 1 PK analyte.
Measure: Measure PY159 Volume at Steady State (Vss) Time: 12 monthsDescription: To evaluate the incidence of anti-drug antibody (ADA) formation to PY159
Measure: Incidence of Anti-Drug Antibody (ADA) formation to PY159 Time: 12 monthsDescription: The incidents of ORR is defined as either a complete or partial response per RECIST. Subjects with no baseline data will be considered no responders. ORR will be summarized by dose, tumor type, and overall. ORR will be summarized descriptively.
Measure: Objective response rate (ORR) Time: 36 monthsDescription: DCR will be measure per resists 1.1 criteria. DCR will be summarized descriptively.
Measure: Deceased control rate (DCR) Time: 36 monthsDescription: DOR will be calculated to determine durability. DOR will be measured from the time by which the criteria for CR or PR-whichever is recorded first-are met until the first date by which recurrent or progressive disease is objectively documented. DOR will be assessed using KAPLAN-MEIER methods.
Measure: Duration of response (DOR) Time: 36 monthsDescription: PFS will be measure from entry onto the study until disease progression or death from any cause. PFS will be assessed using KAPLAN-MEIER methods.
Measure: Progress free survival (PFS) Time: 36 monthsDescription: The duration of overall survival (OS) will be measured from the time of first study drug administration until the date of death. OS will be assessed using KAPLAN-MEIER methods.
Measure: Overall survival (OS) Time: 36 monthsAllocation: Non-Randomized
Sequential Assignment
There is one SNP
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