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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HRS-4642 | Experimental | In Dose Escalation: HRS-4642 will be injected QW. Six dose levels are preset. In Dose Expansion: 1 to 2 dose cohorts will be selected for dose expansion stage. In Indication Expansion: Enrollment into the dose expansion cohorts may be from any eligible solid tumor type. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HRS-4642 | Drug | HRS-4642 will be administrated per dose level in which the patients are assigned. |
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| Measure | Description | Time Frame |
|---|---|---|
| Safety endpoints: adverse events(AEs), serious adverse events(SAEs). | Assess safety and tolerability of HRS-4642 by way of adverse events (CTCAE v5.0). | 24 months |
| Dose Limited Toxicity(DLT) | 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 | from day 1 to Day 21 |
| Maximum tolerated dose (MTD) | Incidence and category of dose limiting toxicities (DLTs) during the first 21-day cycle of HRS-4642 treatment. | From Day 1 to Day 21 |
| RP2D | RP2D will be determined on the basis of evaluation on safety, PK, efficacy data in dose escalation and dose expansion stages. | 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Abnormal Laboratory Values | 24months. | |
| Number of subjects with clinically significant changes in ECOG, vital signs and physical examination. | 24months. | |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Shanghai Pulmonary Hospital | Shanghai | Shanghai Municipality | 200433 | China |
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Single arm study of HRS-4642
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| Number of subjects with changes on ECG. |
| 24months. |
| Efficacy endpoints: Overall response rate (ORR). | Evaluated by RECIST v1.1. | 24months. |
| Efficacy endpoints: Duration of response (DoR). | Evaluated by RECIST v1.1 | 24 months. |
| Efficacy endpoints: Disease control rate (DCR). | Evaluated by RECIST v1.1. | 24months. |
| Efficacy endpoints: Progression free survival (DoR). | Evaluated by RECIST v1.1. | 24months. |
| Efficacy endpoints: overall survival (OS). | Evaluated by RECIST v1.1 | 24minths |
| Cmax. | Maximal plasma concentration. | 24 months. |
| Tmax. | Time to Cmax. | 24 months |
| AUC. | Area under the plasma concentration-time curve. | 24 months. |
| t1/2. | Terminal-phase elimination half-life. | 24 months. |
| Vz/F. | Apparent volume of distribution during terminal phase after non-intravenous administration. | 24 months. |
| CL/F. | Apparent total clearance of the drug from plasma after oral administration. | 24 months. |