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This is a multicenter, open-label phase I clinical trial to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of HS-10541 as monotherapy or in combination with other anti-cancer therapies in participants with KRAS G12C mutation advanced solid tumors.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HS-10541 | Experimental | Participants in all subjects will receive HS-10541 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HS-10541 | Drug | HS-10541 will be administered orally once daily in a continuous regimen |
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| Measure | Description | Time Frame |
|---|---|---|
| Dose-limiting toxicity (DLT) | Number of participants with dose limiting toxicities. | From Cycle 1 Day 1 through Day 21. A cycle is 21 days. |
| Adverse events (AEs) | Incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) from the date of first dose to 28 days (monotherapy) or 90 days (combination therapy) after the final dose (or as specified in the protocol). | Approximately 1.5 years. |
| Objective response rate (ORR) | Defined as the percentage of participants with a best overall response of partial response or better per response evaluation criteria in solid tumors (RECIST 1.1). | Approximately 1.5 years. |
| Progression-free survival (PFS) | Defined as from the date of first dose to the date of disease progression according to investigator assessment or death due to any cause, whichever occurs first. | Approximately 1.5 years |
| Measure | Description | Time Frame |
|---|---|---|
| PK profile of HS-10541as monotherapy, or combination therapy | The maximum concentration (Cmax) | Pre-dose and postdose up to end of treatment, approximately 1.5 years. |
| PK profile of HS-10541as monotherapy, or combination therapy |
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Inclusion Criteria:
Exclusion Criteria:
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Time to the maximum concentration (Tmax)
| Pre-dose and postdose up to end of treatment, approximately 1.5 years |
| PK profile of HS-10541as monotherapy, or combination therapy | Area under the concentration time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC0-t) | Pre-dose and postdose up to end of treatment, approximately 1.5 years |
| PK profile of HS-10541as monotherapy, or combination therapy | Area under the concentration time curve from time zero to infinity (AUC0-∞) | Pre-dose and postdose up to end of treatment, approximately 1.5 years. |
| ORR | Defined as the percentage of participants with a best overall response of partial response or better per response evaluation criteria in solid tumors (RECIST 1.1). | Approximately 1.5 years. |
| Disease control rate (DCR) | Defined as the percentage of participants with a best overall response of stable disease or better per RECIST 1.1. | Approximately 1.5 years. |
| Duration of response (DoR) | Defined as the time from date of first documented evidence of partial response or better to the date of disease progression or death due to any cause | Approximately 1.5 years |
| PFS | Defined as from the date of first dose to the date of disease progression according to investigator assessment or death due to any cause, whichever occurs first. | Approximately 1.5 years |
| Overall Survival (OS) | Defined as the time from date of first dose to the date of death due to any cause | Approximately 3 years. |
| Adverse events (AEs) | Incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) from the date of first dose to 28 days (monotherapy) or 90 days (combination therapy) after the final dose (or as specified in the protocol). | Approximately 1.5 years. |