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This is an open-label, multi-center, multi-cohort, phase Ib/II clinical trial, divided into 8 cohorts according to tumor types. Cohorts 1-4 are SYHA1813 combined with different regimens, including safety run-in stage and cohort expansion stage. Cohorts 5-8 are SYHA1813 monotherapy and only include the expansion cohorts. The primary objective was to evaluate the safety and efficacy of SYHA1813 single agent or in combination with different regimens in unresectable locally advanced or metastatic solid tumors.
In the safety run-in stage, the "3+3" design is used to evaluate the tolerability and safety of different dose levels combined with different regimens, and the observation period of DLT is set as the first treatment cycle. After 3 DLT-evaluable participants at each dose level completed the DLT observation period, the safety of the dose level is evaluated by an SMC consisting of the investigator and the sponsor's medical monitor. Cohorts 1-4 enter the cohort expansion stage after determining the SYHA1813 dose regimen during the safety run-in stage. Cohorts 5-8 enter the cohort expansion stage directly. In the expansion stage, cohorts 1-6 are single-arm studies, the primary endpoint is ORR as evaluated by investigator according to RECIST 1.1. Cohorts 7-8 are randomized controlled studies, the primary endpoint is PFS as evaluated by investigator according to RECIST 1.1.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SYHA1813 single agent or in combination with different regimens | Experimental | Cohorts 1-4 are SYHA1813 combined with different regimens. Cohorts 5-8 are SYHA1813 monotherapy. |
|
| Control group | Active Comparator | The cohort 7 control group is Everolimus. The cohort 8 control group is Regorafenib. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SYHA1813 | Drug | In accordance with the protocol |
|
| Measure | Description | Time Frame |
|---|---|---|
| DLT | Safety run-in stage,Dose-limiting toxicity (DLT) will be assessed according to NCI-CTCAE v5.0. | Up to approximately 2years |
| Frequency and severity of TEAE and SAE | Safety run-in stage | Up to approximately 2years |
| ORR | Cohorts 1-6, Objective response rate (ORR) as evaluated by Investigator (RECIST1.1) | Up to approximately 2 years |
| PFS | Cohorts 7-8, Progression-free survival (PFS) as evaluated by Investigator (RECIST1.1) | Up to approximately 2years |
| Measure | Description | Time Frame |
|---|---|---|
| OS | Overall survival | Up to approximately 2years |
| DoR | Duration of response | Up to approximately 2years |
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Inclusion Criteria:
Aged >= 18 years;
Unresectable locally advanced or metastatic solid tumors confirmed by histology or cytology:
There is at least one measurable lesion in the baseline period (RECIST1.1);
ECOG PS of 0-1;
The expected survival time is >=3 months;
The organ function level and related laboratory indicators must meet the following requirements (No blood transfusion or hematopoietic stimulating factor therapy received within 14 days prior to the first medication (queue 1 to 6)/prior to randomization (queue 7 and queue 8):
ANC≥1.5×10^9/L; PLT≥100×10^9/L(Liver cancer patients PLT≥75×10^9/L); Hb≥90 g/L; TBIL≤1.5×ULN,and for Gilbert's syndrome, liver cancer or liver metastasis patients TBIL≤3×ULN; ALT和AST≤2.5×ULN,for liver cancer or liver metastasis patients ≤5×ULN; Child-Pugh Grade A (only applicable to queue 8); ALB≥30 g/L; Cr≤1.5×ULN,IF Cr>1.5×ULN,Ccr≥60 mL/min(Cockcroft-Gault)is required; APTT and INR≤1.5×ULN
The subjects must agree to take medically approved contraceptive measures for at least 6 months from the beginning of the study to the last dose of drug.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trials Information | Contact | 86-0311-69085587 | ctr-contact@cspc.cn |
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This is an open-label, multi-center, multi-cohort, phase Ib/II clinical trial, divided into 8 cohorts according to tumor types. Cohorts 1-4 are SYHA1813 combined with different regimens, including safety run-in stage and cohort expansion stage. Cohorts 5-8 are SYHA1813 monotherapy and only include the expansion cohorts. In the expansion stage, cohorts 1-6 are single-arm studies, cohorts 7-8 are randomized controlled studies.
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| SG001 | Drug | In accordance with the protocol |
|
| HB1801 | Drug | In accordance with the protocol |
|
| Carboplatin | Drug | In accordance with the protocol |
|
| Cisplatin | Drug | In accordance with the protocol |
|
| Paclitaxel | Drug | In accordance with the protocol |
|
| Etoposide | Drug | In accordance with the protocol |
|
| Everolimus | Drug | In accordance with the protocol |
|
| Regorafenib | Drug | In accordance with the protocol |
|
| DCR | Disease control rate | Up to approximately 2 years |
| Frequency and severity of TEAE and SAE | Safety | Up to approximately 2 years |
| Plasma Concentration | Concentration of SYHA1813/SG001/HB1801 in serum | Up to approximately 2 years |
| Immunogenicity | Incidence of SG001 Anti-drug antibody (ADA) and neutralizing antibody (Nab) (if applicable) | Up to approximately 2 years |
| ID | Term |
|---|---|
| D016190 | Carboplatin |
| D002945 | Cisplatin |
| D017239 | Paclitaxel |
| D005047 | Etoposide |
| D000068338 | Everolimus |
| C559147 | regorafenib |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D011034 | Podophyllotoxin |
| D013764 | Tetrahydronaphthalenes |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D011083 | Polycyclic Compounds |
| D005960 | Glucosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D020123 | Sirolimus |
| D018942 | Macrolides |
| D007783 | Lactones |
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