ST-1898 is a receptor tyrosine kinase (RTK) inhibitor for multi-targets, especially for VEGFR2, c-MET, AXL, PDGFRA, RET, KIT etc. This trial is to evaluate its safety, tolerability, pharmacokinetic, and efficacy in subjects with unresectable or metastatic melanoma. In phase Ib, the primary objectives are to assess the safety and tolerability, and to determine Recommended Phase 2 dose (RP2D) of ST-1898 tablets in subjects with unresectable or metastatic melanoma. Secondary objectives are to assess the plasma concentration of ST-1898 and to evaluate the efficacy. In phase II, the primary objective is to assess the anti-tumor activities of ST-1898 tablets in subjects with unresectable or metastatic melanoma. The secondary objective is to evaluate the safety of ST-1898 tablets.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
64
Supplied as 5 mg and 40 mg tablets
Peking University Cancer Hospital & Institute
Beijing, China
RECRUITINGPhase Ib Dose Escalation: The Number and frequency of treatment-related adverse events (AEs) and treatment related serious adverse events (SAEs)
AEs and SAEs will be assessed according to the National Cancer Institute (NCI) CTCAE v5.0
Time frame: Approximately 18 months
Phase Ib Dose Escalation: Recommended Phase 2 Dose (RP2D)
RP2D was determined according to MTD. MTD was defined as the highest dose level at which no more than 1 in 6 participants experienced a dose-limiting toxicity (DLT) during the first cycle (21days) of treatment.
Time frame: Within the first cycle (21days)
Phase II Expansion: Objective Response Rate (ORR)
ORR is defined as the percentage of participants who experience a CR or PR based on RECIST 1.1 (CR: Complete Response, Disappearance of all target lesions, PR: Partial Response, At least a 30% decrease in the sum of diameters of target lesions)
Time frame: Approximately 18 months
Phase Ib Dose Escalation: Trough concentration of ST-1898
To assess plasma pharmacokinetics (PK) of oral administration of ST-1898
Time frame: Cycle 1 Day 1, Cycle 1 Day 21, Cycle 3 Day 1 during Phase Ib Dose Escalation (21 days per cycle), up to 10 weeks
Phase Ib Dose Escalation: Peak concentration of ST-1898
To assess plasma pharmacokinetics (PK) of oral administration of ST-1898
Time frame: Cycle 1 Day 1, Cycle 1 Day 21, Cycle 3 Day 1 during Phase Ib Dose Escalation (21 days per cycle), up to 10 weeks
Phase Ib Dose Escalation: ORR
Objective Response Rate (ORR) per RECIST 1.1
Time frame: Approximately 18 months
Phase Ib Dose Escalation: PFS
Progression-Free Survival (PFS) per RECIST 1.1
Time frame: Approximately 18 months
Phase Ib Dose Escalation: DoR
DoR Duration of Response (DoR) per RECIST 1.1
Time frame: Approximately 18 months
Phase Ib Dose Escalation: DCR
Disease Control Rate (DCR) per RECIST 1.1
Time frame: Approximately 18 months
Phase Ib Dose Escalation: TTP
Time to Progression per RECIST 1.1
Time frame: Approximately 18 months
Phase II Dose Expansion: The Number and frequency of treatment-related adverse events and serious adverse events (SAEs)
The AEs and SAEs will be assessed according to the National Cancer Institute (NCI) CTCAE v5.0.
Time frame: Approximately 18 months
Phase II Dose Expansion: Trough concentration of ST-1898
To assess plasma Trough concentration of oral administration of ST-1898 in subjects with unresectable or metastatic melanoma
Time frame: Cycle 1 Day 1, Cycle 1 Day 21, Cycle 3 Day 1 during Phase II Dose Expansion (21 days per cycle), up to 10 weeks
Phase II Dose Expansion: Peak concentration of ST-1898
To assess plasma Peak concentration of oral administration of ST-1898 in subjects with unresectable or metastatic melanoma
Time frame: Cycle 1 Day 1, Cycle 1 Day 21, Cycle 3 Day 1 during Phase II Dose Expansion (21 days per cycle), up to 10 weeks
Phase II Dose Expansion: PFS
Progression-Free Survival (PFS) per RECIST 1.1
Time frame: Approximately 18 months
Phase II Dose Expansion: DoR
DoR Duration of Response (DoR) per RECIST 1.1
Time frame: Approximately 18 months
Phase II Dose Expansion: DCR
Disease Control Rate (DCR) per RECIST 1.1
Time frame: Approximately 18 months
Phase II Dose Expansion: TTP
Time to Progression per RECIST 1.1
Time frame: Approximately 18 months
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