Safety and Efficacy of SYHA1813 Single Agent or in Combination With Different Regimens in Unresectable Locally Advanced or Metastatic Solid Tumors.

Phase 1

Not yet recruiting

• Conditions: Unresectable Locally Advanced or Metastatic Solid Tumors
• Interventions: Drug: SYHA1813; Drug: Everolimus; Drug: SG001; Drug: Regorafenib; Drug: HB1801; Drug: Carboplatin; Drug: Cisplatin; Drug: Paclitaxel; Drug: Etoposide

• Registration Number: NCT06682611
• Lead Sponsor: Shanghai Runshi Pharmaceutical Technology Co., Ltd

Brief Summary

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 ...

Detailed Description

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 ...

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Status Verified: 2024-11
• Study First Submitted: 2024-11-08
• Study First Submitted QC: 2024-11-08
• Last Update Submitted: 2024-11-08
• Study First Posted: 2024-11-11
• Last Update Posted: 2024-11-11
• Study Start: 2024-11-13
• Primary Completion: 2026-11-13
• Study Completion: 2027-11-13

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 380

Inclusion Criteria

1. Aged >= 18 years;

2. Unresectable locally advanced or metastatic solid tumors confirmed by histology or cytology:

3. There is at least one measurable lesion in the baseline period (RECIST1.1);

4. ECOG PS of 0-1;

5. The expected survival time is >=3 months;

6. 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

7. 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.

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Exclusion Criteria

1. Patients who are known or suspected to be allergic to the test drug or its components;
2. Excluding the disease studied in this trial, there are other primary malignant tumors that have progressed or require treatment within the past 3 years prior to screening (except for effectively controlled skin basal cell carcinoma, cutaneous squamous cell carcinoma, superficial bladder cancer or cured breast carcinoma in situ);
3. The toxicity of previous anti-tumor treatments has not recovered (≤grode 1), except for hair loss and other adverse reactions judged by the investigator that do not affect the safety of the study medication;
4. Active leptomeningeal disease or CNS metastases that are not well controlled;
5. Uncontrollable active infections occurred within 14 days prior to the first medication (queue 1 to 6)/prior to randomization (queue 7 and queue 8), requiring systemic treatment with intravenous antibiotic infusion
6. Patients with evidence of bleeding tendency or medical history within 28 days;
7. Patients have risk factors for intestinal obstruction or intestinal perforation;
8. The subject has poorly healed wounds, ulcers or fractures;
9. Urine protein ≥ 2+, and 24-hour urine protein quantitative ≥ 1.0g/24h;
10. Patients have large pleural effusions, pericardial effusions, or abdominopelvic effusions;
11. Human immunodeficiency virus (HIV) antibody positive; active hepatitis C, with antibody positive and HCV RNA test positive; active hepatitis B, with HBsAg positive, and HBV-DNA value>500 IU/ml or 2500 copies/mL;
12. Has a history of active tuberculosis;
13. History of interstitial lung disease (except for radiotherapy-induced focal interstitial pneumonia), noninfectious pneumonitis requiring glucocorticoid therapy;
14. Received immunosuppressants such as PD-1 or PD-L1 inhibitors in the recurrent or metastatic phase (only for Cohort 1);
15. Prior treatment with a VEGFR-TKI inhibitor or other anti-angiogenic agent (except for Cohort 5,7,8);
16. Pregnant or lactating women;
17. Participants who may have poor compliance as judged by the investigator, such as a clear history of neurological or psychiatric disorders (including epilepsy or dementia), current psychiatric disorders, psychotropic drug abuse, etc.;

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SYHA1813 single agent or in combination with different regimens	SYHA1813	Cohorts 1-4 are SYHA1813 combined with different regimens. Cohorts 5-8 are SYHA1813 monotherapy.
SYHA1813 single agent or in combination with different regimens	Everolimus	Cohorts 1-4 are SYHA1813 combined with different regimens. Cohorts 5-8 are SYHA1813 monotherapy.
SYHA1813 single agent or in combination with different regimens	Regorafenib	Cohorts 1-4 are SYHA1813 combined with different regimens. Cohorts 5-8 are SYHA1813 monotherapy.
Control group	SYHA1813	The cohort 7 control group is Everolimus. The cohort 8 control group is Regorafenib.
Control group	SG001	The cohort 7 control group is Everolimus. The cohort 8 control group is Regorafenib.
Control group	HB1801	The cohort 7 control group is Everolimus. The cohort 8 control group is Regorafenib.
Control group	Carboplatin	The cohort 7 control group is Everolimus. The cohort 8 control group is Regorafenib.
Control group	Cisplatin	The cohort 7 control group is Everolimus. The cohort 8 control group is Regorafenib.
Control group	Paclitaxel	The cohort 7 control group is Everolimus. The cohort 8 control group is Regorafenib.
Control group	Etoposide	The cohort 7 control group is Everolimus. The cohort 8 control group is Regorafenib.
Control group	Everolimus	The cohort 7 control group is Everolimus. The cohort 8 control group is Regorafenib.
Control group	Regorafenib	The cohort 7 control group is Everolimus. The cohort 8 control group is Regorafenib.

Primary Outcome Measures

Name	Time	Method
DLT	Up to approximately 2years	Safety run-in stage，Dose-limiting toxicity (DLT) will be assessed according to NCI-CTCAE v5.0.
Frequency and severity of TEAE and SAE	Up to approximately 2years	Safety run-in stage
ORR	Up to approximately 2 years	Cohorts 1-6, Objective response rate (ORR) as evaluated by Investigator (RECIST1.1)
PFS	Up to approximately 2years	Cohorts 7-8, Progression-free survival (PFS) as evaluated by Investigator (RECIST1.1)

Secondary Outcome Measures

Name	Time	Method
OS	Up to approximately 2years	Overall survival
DoR	Up to approximately 2years	Duration of response
DCR	Up to approximately 2 years	Disease control rate
Frequency and severity of TEAE and SAE	Up to approximately 2 years	Safety
Plasma Concentration	Up to approximately 2 years	Concentration of SYHA1813/SG001/HB1801 in serum
Immunogenicity	Up to approximately 2 years	Incidence of SG001 Anti-drug antibody (ADA) and neutralizing antibody (Nab) (if applicable)