Advanced KRAS G12D Mutant Solid Tumors
Conditions
Brief summary
This is an open-label, multi-center phase I clinical study to evaluate HRS-6093 Safety, Tolerability, and Pharmacokinetics in Participants harboring KRAS G12D Mutations with advanced solid tumors. The study consists of dose escalation, dose expansion and efficacy expansion.
Interventions
DRUGHRS-6093
HRS-6093
Sponsors
Jiangsu HengRui Medicine Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Have fully understood this study and are willing to sign the ICF, with good compliance and cooperation in follow-up; 2. Aged between 18-75 years, with no gender requirement; 3. Participants with histologically/cytologically confirmed advanced solid tumors who have been previously tested or are confirmed by the central laboratory to harbor KRAS G12D mutations; Have failed standard treatment, are intolerant to standard treatment, or have not received standard treatment. 4. ECOG performance status (PS) score of 0 or 1; 5. Life expectancy \> 3 months; 6. At least one measurable lesion per RECIST v1.1; A tumor tissue sample must be provided. 7. Adequate organ function
Exclusion criteria
1. Toxicity (e.g., gastrointestinal reaction and skin toxicity) from prior anti-tumor treatment has not recovered to Grade ≤ 1 or a level specified in the inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and severity of adverse events/serious adverse events (graded as per CTCAE v5.0). | Screening Period to 30 Days After the Last Dose |
| DLT, | from day1 to day 23; 23 Days |
| MTD, | from day1 to day 23; 23 Days |
| RP2D , | 24 months |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Abnormal Laboratory Values | Screening Period to 30 Days After the Last Dose; 24 months |
| Number of subjects with clinically significant changes in ECOG, vital signs and physical examination. | Screening Period to 30 Days After the Last Dose; 24 months |
| Number of subjects with changes on ECG. | Screening Period to 30 Days After the Last Dose; 24 months |
| maximum plasma concentration (Cmax), | Screening Period to Day of the end of treatment/withdrawal. 24 months |
| time to maximum concentration (Tmax), | Screening Period to Day of the end of treatment/withdrawal. 24 months |
| duration of response (DoR), | Screening Period to PD; 24 months |
| area under the blood concentration-time curve at steady state (AUCss), and accumulation ratio (Rac); | Screening Period to Day of the end of treatment/withdrawal. 24 months |
| Area under concentration-time curve from time 0 to infinity (AUC 0-∞), apparent volume of distribution (Vz/F), | Screening Period to Day of the end of treatment/withdrawal. 24 months |
| elimination half-life (t1/2), and apparent clearance (CL/F); | Screening Period to Day of the end of treatment/withdrawal. 24 months |
| minimum concentration at steady state (Cmin, ss), | Screening Period to Day of the end of treatment/withdrawal. 24 months |
| objective response rate (ORR), | Screening Period to PD; 24 months |
| area under concentration-time curve from time 0 to the last measurable concentration time point t (AUC0-t), | Screening Period to Day of the end of treatment/withdrawal. 24 months |
| disease control rate (DCR), | Screening Period to PD; 24 months |
| progression-free survival (PFS), | Screening Period to PD; 24 months |
| overall survival (OS). | Screening Period to Day of death of the participant;24months |
Countries
China
Contacts
Primary ContactRongfu Mao
Backup ContactJizhao Li
Outcome results
None listed