This is a multi-center , open-label, phase 1/2 study to evaluate the safety, efficacy, and pharmacokinetic (PK) characteristics of HYP-6589 in monotherapy in advanced solid tumors and combination with tyrosine kinase inhibitors in patients with advanced NSCLC with target-driven gene positivity.
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 HYP-6589 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
115
HYP-6589 should be administered orally at the recommended dosage
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, 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.
Time frame: 24 days during the first 4-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 Escalation (Part One): Other safety indicators
Adverse events (AE), physical examination, vital signs, electrocardiogram (ECG) and laboratory test results that occur during the treatment
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 Expansion (Part Two): Other safety indicators
Adverse events (AE), physical examination, vital signs, electrocardiogram (ECG) and laboratory test results that occur during the treatment.
Time frame: Up to 2 years
Dose Escalation and Expansion: Assessment of HYP-6589 Cmax
Maximum concentration observed (Cmax) observed from the pharmacokinetic profile
Time frame: Up to 2 years
Dose Escalation and Expansion: Assessment of HYP-6589 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 HYP-6589 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 HYP-6589 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 HYP-6589 to death due to any cause
Time frame: Up to 2 years
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