A Study of CS1001 in Combination With Donafenib in Subjects With Advanced Solid Tumors

Study Overview
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Brief Summary
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This study will evaluate the safety, tolerability, pharmacokinetics and treatment effect of CS1001 in combination with Donafenib in patients with advanced solid tumors.

Detailed Description
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This trail uses an open, multi-center study design, Contains two parts: a dose escalation part and a dose expansion part.

Official Title
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A Phase I, Multicenter,Open-label,Dose-Escalation and Expansion Study of CS1001 in Combination With Donafenib in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: Donafenib
* Drug: CS1001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fully understand this study and voluntarily sign ICF; 18 to 75 years old (including 18 and 75 years old), male or female; Subjects with advanced solid tumors, including: Phase I study: subjects with advanced solid tumors confirmed by histology or cytology that are not suitable for surgical resection, or have failed or tolerated standard treatment, or have no standard treatment. Including but not limited to Cholangiocarcinoma , head and neck squamous cell carcinoma (HNSCC) and endometrial cancer. Exclusion Criteria: Any history of active autoimmune diseases or autoimmune diseases; patients with vitiligo or asthma that has been completely relieved in childhood, and patients who do not need any intervention after adulthood can be included; Participants with any condition that impairs their ability to take oral medication, such as lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome. Patients with uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage and need to retain a catheter; Human immunodeficiency virus (HIV) antibody positive; Patients who are simultaneously infected with hepatitis B virus and hepatitis C virus; Lactating women. If they are willing to stop breastfeeding, they can also be included in this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cholangiocarcinoma<br>Cholangiocarcinoma | Drug: Donafenib<br>* dose escalation: Donafenib 100 mg QD/100 mg BID/200 mg BID (p.o.). dose expansion: Patients will be assigned to specific tumor types and treated at the recommended dose for dose escalation.The recommended dose for dose escalation will be determined by the dose escalation study.<br>Drug: CS1001<br>* CS1001 will be administrated by intravenous (i.v.) infusion once every 28 days<br>|
| Experimental: Squamous cell carcinoma of the head and neck<br>Squamous cell carcinoma of the head and neck（HNSCC） | Drug: Donafenib<br>* dose escalation: Donafenib 100 mg QD/100 mg BID/200 mg BID (p.o.). dose expansion: Patients will be assigned to specific tumor types and treated at the recommended dose for dose escalation.The recommended dose for dose escalation will be determined by the dose escalation study.<br>Drug: CS1001<br>* CS1001 will be administrated by intravenous (i.v.) infusion once every 28 days<br>|
| Experimental: Endometrial cancer<br>Endometrial cancer | Drug: Donafenib<br>* dose escalation: Donafenib 100 mg QD/100 mg BID/200 mg BID (p.o.). dose expansion: Patients will be assigned to specific tumor types and treated at the recommended dose for dose escalation.The recommended dose for dose escalation will be determined by the dose escalation study.<br>Drug: CS1001<br>* CS1001 will be administrated by intravenous (i.v.) infusion once every 28 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events |  | From the day of first dose to 21 days after last dose | 
| To determine the dose limiting toxicity (DLT) |  | In the dose escalation part, from the day of first dose to 21 days after last dose | 
| To determine the maximum tolerated dose(MTD) |  | In the dose escalation part, from the day of first dose to 21 days after last dose | 
| To determine the recommended dose of phase II |  | In the dose escalation part, from the day of first dose to 21 days after last dose | 
| Objective response rate as determined by the Invertigator using RECIST V1.1 |  | In the dose escalation part, from the day of first dose to 21 days after last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-CS1001 antibody |  | From the day of first dose to 21 days after last dose | 
| Objective response rate (ORR) |  | From the day of first dose to 21 days after last dose | 
| Overall survival(OS) |  | From the day of first dose to 21 days after last dose | 
| Progression free survival(PFS) |  | From the day of first dose to 21 days after last dose | 
| Duration of remission (DOR) |  | From the day of first dose to 21 days after last dose |