This is a multicenter, open-label, phase I/Ⅱ study to evaluate the safety, efficacy, and pharmacokinetic (PK)/pharmacodynamic(PD) characteristics of HY0001a for injection in participants with advanced solid tumors.
This is a first-in-human (FIH), Phase I/II, open-label, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of HY0001a for injection in patients with advanced/metastatic solid tumors. HY0001a for injection is administered via intravenous infusion using an accelerated titration method followed by a conventional 3 + 3 study design to identify the maximum tolerated dose (MTD) and dose-limiting toxicities(DLT). In addition, the maximum-tolerated dose and recommended Phase II dose for HY0001a for injection will be determined.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
HY0010a for injection should be administered at the recommended dosage
Peking University Cancer Hospital
Beijing, Beijing Municipality, China
Dose 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.
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
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
Time frame: Up to 2 years
Dose Escalation and Expansion: Assessment of HY0001a for injection, HY0001a-TAb, and free monomethyl auristatin E (MMAE, i.e., the toxin) Cmax
Maximum concentration observed (Cmax) observed from the pharmacokinetic profile
Time frame: Up to 2 years
Dose Escalation and Expansion: Assessment of HY0001a for injection, HY0001a-TAb, and free MMAE (i.e., the toxin) AUC
Area under the concentration versus time curve calculated using the trapezoidal method
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Time frame: Up to 2 years
Dose Escalation and Expansion: Assessment of HY0001a for injection, HY0001a-TAb, and free MMAE (i.e., the toxin) 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 (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 HY0001a 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: Overall Survival (OS)
Overall Survival (OS) is defined as the time from the date of first administration of HY0001a to death due to any cause
Time frame: Up to 2 years
Immunogenicity assessment indicator: Anti-drug antibodies (ADA)
Incidence, duration, titer of serum anti-HY0001a ADA
Time frame: Up to 2 years