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This phase I trial is designed to efficiently identify the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) for the combination therapy regimen of the IDO1 inhibitor SHR9146 when administered in combination with immune checkpoint PD-1 inhibitor SHR-1210 plus VEGFR inhibitor Apatinib or not in subjects with advanced/metastatic solid tumors. All subjects will receive the same standard SHR-1210 plus Apatinib (only three drugs group)regimen, while SHR9146 in doses increasing from 100 mg twice daily to, potentially, 600 mg twice daily. Once the recommended regimen has been identified, subjects with the selected tumor type will be enrolled into expansion cohorts based upon prior safety and tolerability data.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 2 drugs combination group | Experimental |
| |
| 3 drugs combination group | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SHR9146+SHR-1210 | Drug | SHR9146: Initial dose of 100mg BID with escalation planned to 600mg BID; SHR-1210: 200mg Q2W |
|
| Measure | Description | Time Frame |
|---|---|---|
| DLT | Baseline through 27/28 days | |
| MTD | Baseline through 27/28 days |
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Inclusion Criteria:
Subjects with histologically or cytologically confirmed advanced or metastatic solid tumors that have failed prior standard therapy (including subject refusal or intolerance).
At least one measurable parameter according to RECIST 1.1.
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
Life expectancy of at least 12 weeks.
Subjects must have normal organ and marrow function as defined below:
Subjects with known brain metastases will only be eligible after their tumors have been treated with definitive resection and/or radiotherapy and they are neurologically stable for at least two months apart and at least 1 month off steroids.
Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ying Cheng, Prof. | Jilin Provincial Tumor Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Jilin Province Cancer Hospital | Changchun | Jilin | 130012 | China |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D009362 | Neoplasm Metastasis |
| ID | Term |
|---|---|
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| SHR9146+SHR-1210+Apatinib | Drug | SHR9146: Initial dose of 100mg BID with escalation planned to 600mg BID; SHR-1210: 200mg Q2W Apatinib:250mg QD |
|