Advanced KRAS G12D Mutant Solid Tumors
Conditions
Brief summary
The study is being conducted to evaluate the safety and tolerability of HRS-4642 in patients with advanced solid tumors harboring KRAS G12D mutation.To estimate the maximum tolerated dose (MTD) and/or a biologically active dose (eg, recommended phase 2 dose \[RP2D\]) within investigated subject population groups
Interventions
DRUGHRS-4642
HRS-4642 will be administrated per dose level in which the patients are assigned.
Sponsors
Jiangsu HengRui Medicine Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single arm study of HRS-4642
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects must voluntarily agree to participate in the trial and sign a written informed consent form. 2. Male or female ≥ 18 years old. 3. Histologically confirmed diagnosis of advanced solid tumor harbouring with KRAS G12D mutation 4. ECOG performance status of 0-1. 5. With a life expectancy of ≥3 months. 6. Have at least one measurable lesion. 7. Adequate laboratory parameters during the screening period
Exclusion criteria
1. Previously received KRAS G12D inhibitors 2. Priot radiotherapy within 28 days for non-thoracic radiation 3. Prior anti-tumor chemotherapy (\< 6 weeks if chemotherapy including nitrosoureas or mitomycin) within 4 weeks before the study drug administration 4. Any unresolved AEs \> Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety endpoints: adverse events(AEs), serious adverse events（SAEs）. | 24 months | Assess safety and tolerability of HRS-4642 by way of adverse events (CTCAE v5.0). |
| Dose Limited Toxicity(DLT) | from day 1 to Day 21 | A DLT is defined as any event meeting the DLT criteria occurring within 21 days of first dose on Cycle 1 Day 1 (C1D1), excluding toxicities clearly related to disease progression or intercurrent illness |
| Maximum tolerated dose (MTD) | From Day 1 to Day 21 | Incidence and category of dose limiting toxicities (DLTs) during the first 21-day cycle of HRS-4642 treatment. |
| RP2D | 24 months | RP2D will be determined on the basis of evaluation on safety, PK, efficacy data in dose escalation and dose expansion stages. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy endpoints: Duration of response (DoR). | 24 months. | Evaluated by RECIST v1.1 |
| Efficacy endpoints: Disease control rate (DCR). | 24months. | Evaluated by RECIST v1.1. |
| Efficacy endpoints: Progression free survival (DoR). | 24months. | Evaluated by RECIST v1.1. |
| Efficacy endpoints: overall survival (OS). | 24minths | Evaluated by RECIST v1.1 |
| Cmax. | 24 months. | Maximal plasma concentration. |
| Number of Participants With Abnormal Laboratory Values | 24months. | — |
| AUC. | 24 months. | Area under the plasma concentration-time curve. |
| t1/2. | 24 months. | Terminal-phase elimination half-life. |
| Vz/F. | 24 months. | Apparent volume of distribution during terminal phase after non-intravenous administration. |
| CL/F. | 24 months. | Apparent total clearance of the drug from plasma after oral administration. |
| Tmax. | 24 months | Time to Cmax. |
| Number of subjects with clinically significant changes in ECOG, vital signs and physical examination. | 24months. | — |
| Number of subjects with changes on ECG. | 24months. | — |
| Efficacy endpoints: Overall response rate (ORR). | 24months. | Evaluated by RECIST v1.1. |
Countries
China
Outcome results
None listed