This is a multi-center, open-label, phase 1/2 study to evaluate the safety, efficacy, and pharmacokinetic (PK)/pharmacodynamic (PD) characteristics of HY07121 in participants with advanced solid tumors.
The study starts with a dose escalation part (Part 1) followed by a dose expansion part (Part 2). The main purpose of this study is to evaluate the safety and tolerability of the drug HY07121 and determine the maximum tolerated dose (MTD) (if any) and/or the recommended dose(s) (RD) and preliminary anti-tumor activity. Additional purposes of the study are to evaluate the pharmacokinetics (PK) properties, immunogenicity, correlation of the biomarkers and PK profile with anti-tumor activity.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
258
HY07121 should be administered intravenously at recommended dose.
Cancer Hospital of Shandong First Medical University
Jinan, China
RECRUITINGDose Escalation (Part One): Incidence and Nature of Dose-Limiting Toxicity (DLT)
Dose-Limiting Toxicity (DLT) will be defined using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 or American Society for Transplantation and Cellular Therapy (ASTCT) criteria for Cytokine Release Syndrome (CRS).
Time frame: 21 days during the first 3-week cycle
Dose Escalation (Part One): Percentage of participants experiencing treatment-emergent adverse events (TEAEs)
Incidence and severity of adverse events (AEs), serious adverse events (SAEs), and lab abnormalities, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading
Time frame: Up to 2 years
Dose Escalation (Part One): Percentage of participants experiencing Adverse Event (AE) related dose interruptions, dose delays, and dose intensity
Occurrence of Adverse Event (AE) related dose interruptions, dose delays and dose intensity (duration of HY07121 exposure)
Time frame: Up to 2 years
Dose Expansion (Part Two): Objective Response Rate (ORR)
Proportion of participants who have a confirmed Complete Response (CR) or a Partial Response (PR)
Time frame: Up to 2 years
Dose Expansion (Part Two): Percentage of participants experiencing treatment-emergent adverse events (TEAEs)
Incidence and severity of adverse events (AEs), serious adverse events (SAEs), and lab abnormalities, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading
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Time frame: Up to 2 years
Dose Expansion (Part Two): Percentage of participants experiencing adverse event (AE) related dose interruptions, dose delays, and dose intensity
Occurrence of adverse event (AE) related dose interruptions, dose delays and dose intensity (duration of HY07121 exposure).
Time frame: Up to 2 years
Dose Escalation and Expansion: Assessment of HY07121 Cmax
Maximum concentration observed (Cmax) observed from the pharmacokinetic profile
Time frame: Up to 2 years
Dose Escalation and Expansion: Assessment of HY07121 AUC
Area under the concentration versus time curve calculated using the trapezoidal method
Time frame: Up to 2 years
Dose Escalation and Expansion: Assessment of HY07121 T1/2
The time it takes for half the drug concentration to be eliminated calculated using slope of the terminal line
Time frame: Up to 2 years
Dose Escalation and Expansion: Assessment of HY07121 anti-drug-antibody (ADA)
Incidence, duration, titer of serum anti-HY07121 antibody (ADA)
Time frame: Up to 2 years
Dose Escalation (Part One): Objective Response Rate (ORR)
Proportion of participants who have a confirmed complete response (CR) or a Partial Response (PR) determined by Investigator per the Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1
Time frame: Up to 2 years
Dose Escalation and Expansion: Duration Of Response (DOR) assessed by investigator per Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1
Duration Of Response (DOR) is defined as the time from the measurement criteria are first met for complete response (CR) /Partial Response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease.
Time frame: Up to 2 years
Dose Escalation and Expansion: Disease Control Rate (DCR) assessed by investigator per RECIST Version 1.1
Disease Control Rate is defined as the percentage of participants who have achieved CR or PR or have demonstrated stable disease
Time frame: Up to 2 years
Dose Escalation and Expansion: Progression-Free Survival (PFS) assessed by investigator per RECIST Version 1.1
Progression-Free Survival (PFS) is defined as the time from the date of first administration of HY07121 to the date of the first documented disease progression determined by Investigator as per RECIST 1.1 or death from any cause, whichever occurs first
Time frame: Up to 2 years
Dose Escalation and Expansion: Time-To-Progression (TTP) assessed by investigator per RECIST Version 1.1
Time-To-Progression (TTP) is defined as the time from the date of first administration of HY07121 to the date of the first documented disease progression
Time frame: Up to 2 years
Dose Escalation and Expansion: Overall Survival (OS)
Overall Survival (OS) is defined as the time from the date of first administration of HY07121 to death due to any cause
Time frame: Up to 2 years
Dose Escalation and Expansion: The correlation between tumor biomarkers and efficacy
Objective Response Rate (ORR) is defined as proportion of participants who have a confirmed Complete Response (CR) or a Partial Response (PR) determined by Investigator per RECIST version 1.1. Tumor biomarkers will be tested using Immunohistochemistry (IHC) and scored using Tumor Proportion Score (TPS) and/or Combined Positive Score (CPS) algorithm.
Time frame: Up to 2 years