This study employs a non-randomized, open-label design to evaluate the safety, tolerability, pharmacokinetic (PK) profile, and preliminary efficacy of DC50292A tablets in patients with MTAP-deficient advanced or metastatic solid tumors. The study consists of two parts: dose escalation and dose expansion.
Dose Escalation Phase: The dose escalation study will first be conducted using an accelerated titration "3+3" design, progressing from lower to higher dose levels. Six dose groups are planned: 40 mg, 100 mg, 200 mg, 400 mg, 600 mg, and 900 mg (subject to adjustment based on study results, such as adding intermediate dose levels). The 40 mg group will follow an accelerated titration design, enrolling 1-6 subjects, while the 100-900 mg groups will enroll 3-6 subjects per cohort. Each dose group will undergo: Single-dose administration (C0D1-C0D5): A single dose on C0D1, followed by PK blood sampling from C0D2 to C0D5. Cycle 1 (C1D1-C1D21): Starting from C1D1 (after C0D5), subjects will receive daily dosing for 3 weeks, followed by a 3-day break (until C1D25 pre-dose) for dose-limiting toxicity (DLT) assessment, along with PK and pharmacodynamic (PD) sample collection and analysis. Subsequent cycles (C2D1-CnD28): Continuous dosing in subsequent cycles, with adjustments and optimizations based on cumulative safety, PK, and PD data. If no DLT-based stopping criteria are met during the observation period, the dose will escalate to the next level. After the DLT observation period, eligible subjects may continue treatment with DC50292A until disease progression, intolerable toxicity, initiation of new antitumor therapy, withdrawal of consent, voluntary discontinuation, death, loss to follow-up, or other protocol-specified termination criteria-whichever occurs first. Dose Expansion Phase: after determining the maximum tolerated dose (MTD) in the escalation phase, two optimal doses (≤MTD) will be selected for expansion based on cumulative efficacy, safety, and PK data. Each expansion cohort will enroll 8 subjects, receiving oral DC50292A in an optimized regimen (tentatively once daily in 4-week cycles) until meeting discontinuation criteria (as above).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
32
DC50292A tablet
Fujian Cancer Hospital
Fuzhou, Fujian, China
RECRUITINGSun Yat-Sen University Cancer Center
Guangzhou, Guangdong, China
RECRUITINGGuangxi Medical University Cancer Hospital
Nanning, Guangxi, China
Number of Participants With Adverse Events
Incidence and severity of adverse events as assessed by CTCAE Version 5.0
Time frame: 12 months
PK profile of DC50292A
Peak Concentration (Cmax): The maximum plasma concentration of the drug.
Time frame: From time zero up to 96 hours post-dose
PK profile of DC50292A
Area Under the Curve from Time Zero to the Last Measurable Concentration (AUC0-t): The area under the plasma concentration-time curve from time zero to the last measurable concentration.
Time frame: From time zero up to 96 hours post-dose
PK profile of DC50292A
Area Under the Curve from Time Zero Extrapolated to Infinity (AUC0-∞): The area under the plasma concentration-time curve from time zero extrapolated to infinity.
Time frame: From time zero up to 96 hours post-dose
PK profile of DC50292A
Time to Reach Peak Concentration (Tmax): The time at which the peak plasma concentration is reached.
Time frame: From time zero up to 96 hours post-dose
PK profile of DC50292A
Elimination Half-Life (T1/2): The time required for the plasma concentration to decrease by half.
Time frame: From time zero up to 96 hours post-dose
Overall response rate (ORR)
Overall response rate (ORR) based on RECIST v1.1 as assessed by the investigator
Time frame: Up to 12 months
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Harbin Medical University Cancer Hospital
Harbin, Heilongjiang, China
RECRUITINGHenan Cancer Hospital
Zhengzhou, Henan, China
RECRUITINGHunan Cancer Hospital
Changsha, Hunan, China
RECRUITINGShandong Cancer Hospital
Jinan, Shandong, China
RECRUITINGSir Run Run Shaw Hospital
Hangzhou, Zhejiang, China
RECRUITINGProgression-free Survival (PFS)
Progression-free survival (PFS) based on RECIST v1.1 as assessed by the investigator
Time frame: Up to 12 months