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The primary objectives of this study are to characterize the safety and tolerability of CS23546 and to evaluate the pharmacokinetic (PK) characteristics and recommended phase 2 dose (RP2D) of CS23546 in subjects with advanced tumors.
This study is a single arm, open phase I trial, consisting of a dose escalation phase (single dose+multiple doses) and a dose expansion phase, accompanied by pharmacokinetic and pharmacokinetic studies. The first visit period (21 days) of single dose and multiple doses during the dose-increasing phase is the DLT observation period.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose escalation | Experimental | Single ascending dose (SAD): Participants will receive CS23546 once on the first day (D1). Multiple ascending dose (MAD): Participants will receive CS23546 once daily from the 7th day (C1D1). |
|
| Dose expansion | Experimental | Dose expansion is planned to begin when the recommended Phase 2 dose (RP2D) will be determined. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CS23546 | Drug | Tablets administered orally. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Dose Limiting Toxicities (DLTs) | DLT: Number of patients experienced any dose limited toxicity. MTD: One level lower than the dose level at which dose escalation was terminated due to DLT reasons. | Day 1 through Day 27 |
| Maximum Tolerated Dose (MTD) | MTD: One level lower than the dose level at which dose escalation was terminated due to DLT reasons. | Day 1 through Day 27 |
| Time to Cmax (Tmax) | Time to reach the Cmax for CS23546. | up to Day 1 of cycle 5 (each cycle is 21 days) |
| Maximum plasma concentration (Cmax) | Maximum observed plasma concentration for CS23546. | up to Day 1 of cycle 5 (each cycle is 21 days) |
| Area Under the Curve (AUC) | Area Under the Plasma Concentration-time Curve From Zero Time to the Last Measurable Point for CS23546. | up to Day 1 of cycle 5 (each cycle is 21 days) |
| Measure | Description | Time Frame |
|---|---|---|
| The inhibitory activity of Programmed cell death 1 ligand 1 (PD-L1) | up to Day 1 of cycle 5 (each cycle is 21 days) | |
| Interferon gamma (IFN-γ) | Plasma concentration for IFN-γ. | up to Day 1 of cycle 5 (each cycle is 21 days) |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Xinhao Wang | Contact | +86 0755-36993550 | xinhwang@chipscreen.com |
| Name | Affiliation | Role |
|---|---|---|
| Huiqiang Huang, Ph.D. | Sun Yat-sen University Cancer Cancer | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sun Yat-sen University Cancer Cancer | Recruiting | Guangzhou | China |
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| Free PD-L1 | Plasma concentration for free PD-L1. | up to Day 1 of cycle 5 (each cycle is 21 days) |
| C-X-C motif chemokine 9 (CXCL9) | Plasma concentration for CXCL9. | up to Day 1 of cycle 5 (each cycle is 21 days) |
| C-X-C motif chemokine 10 (CXCL10) | Plasma concentration for CXCL10. | up to Day 1 of cycle 5 (each cycle is 21 days) |
| Objective response rate (ORR) | Efficacy evaluation indicators for research. | Until 28 days after the last dose of the study drug |
| Disease control rate (DCR) | Efficacy evaluation indicators for research. | Until 28 days after the last dose of the study drug |
| Duration of response (DOR) | Efficacy evaluation indicators for research. | Until 28 days after the last dose of the study drug |
| Time to progression (TTP) | Efficacy evaluation indicators for research. | Until 28 days after the last dose of the study drug |
| time to progressive disease (TTR) | Efficacy evaluation indicators for research. | Until 28 days after the last dose of the study drug |
| Progression free survival (PFS) | Efficacy evaluation indicators for research. | Until 28 days after the last dose of the study drug |
| Overall survival (OS) | Efficacy evaluation indicators for research. | Until 28 days after the last dose of the study drug |
| Safety indicators: adverse events (AE) | The incidence and severity of adverse events (AE) (according to CTCAE v5.0). | Until 28 days after the last dose of the study drug |