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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
636
HS-10541 will be administered orally once daily in a continuous regimen
Dose-limiting toxicity (DLT)
Number of participants with dose limiting toxicities.
Time frame: 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).
Time frame: 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).
Time frame: 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.
Time frame: Approximately 1.5 years
PK profile of HS-10541as monotherapy, or combination therapy
The maximum concentration (Cmax)
Time frame: Pre-dose and postdose up to end of treatment, approximately 1.5 years.
PK profile of HS-10541as monotherapy, or combination therapy
Time to the maximum concentration (Tmax)
Time frame: 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)
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Time frame: 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-∞)
Time frame: 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).
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: 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
Time frame: 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).
Time frame: Approximately 1.5 years.