KRAS G12C Mutation Advanced Solid Tumor
Conditions
Brief summary
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.
Interventions
DRUGHS-10541
HS-10541 will be administered orally once daily in a continuous regimen
Sponsors
Jiangsu Hansoh Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Voluntary participation and written informed consent.. 2. Aged 18 years or older (≥18 years), of any gender. 3. Histologically or cytologically confirmed advanced solid tumor. 4. At least one measurable lesion according to RECIST v1.1. 5. ECOG PS of 0 to 1, with no deterioration within 2 weeks prior to the first dose. 6. With a life expectancy \> 12 weeks. 7. Adequate bone marrow reserve and organ function. 8. Female participants of childbearing potential and non-sterilized male participants must agree to use highly effective contraceptive measures from the time of signing the ICF until 6 months after the last dose. 9. Female participants of childbearing potential must be non-lactating; all female participants must have a negative pregnancy test prior to the first dose.
Exclusion criteria
1. Uncontrolled pleural effusion, pericardial effusion, or abdominal effusion requiring clinical intervention. 2. Presence of symptomatic brain metastases, leptomeningeal/brainstem involvement, history of intracranial hemorrhage or intraspinal hemorrhage, or spinal cord compression. 3. Unresolved CTCAE ≥grade 2 toxicities from previous anticancer therapy. 4. History of a second primary malignancy 5. Severe, uncontrolled, or active cardiovascular or cerebrovascular diseases, or severe cardiac examination abnormalities. 6. Severe or poorly controlled diabetes mellitus or hypertension. 7. Known active infectious diseases. 8. Clinically significant gastrointestinal dysfunction. 9. Gastrointestinal obstruction or perforation occured. 10. Interstitial lung disease (ILD). 11. Participants with known hypersensitivity or contraindications to any active or inactive ingredients of the study drug, chemically similar drugs, or drugs of the same class. 12. Other inappropriate situation considered by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting toxicity (DLT) | From Cycle 1 Day 1 through Day 21. A cycle is 21 days. | Number of participants with dose limiting toxicities. |
| Adverse events (AEs) | Approximately 1.5 years. | 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). |
| Objective response rate (ORR) | Approximately 1.5 years. | 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). |
| Progression-free survival (PFS) | Approximately 1.5 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK profile of HS-10541as monotherapy, or combination therapy | Pre-dose and postdose up to end of treatment, approximately 1.5 years. | The maximum concentration (Cmax) |
| ORR | Approximately 1.5 years. | 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). |
| Disease control rate (DCR) | Approximately 1.5 years. | Defined as the percentage of participants with a best overall response of stable disease or better per RECIST 1.1. |
| Duration of response (DoR) | Approximately 1.5 years | 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 |
| PFS | Approximately 1.5 years | 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. |
| Overall Survival (OS) | Approximately 3 years. | Defined as the time from date of first dose to the date of death due to any cause |
| Adverse events (AEs) | Approximately 1.5 years. | 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). |
Outcome results
None listed