A Study of CS1003 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, pharmacokinetic profile and treatment effect of a new drug known as CS1003 in patients with advanced tumors.

Official Title
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A Phase Ia/Ib, Open-Label, Multiple-Dose, Dose-Escalation and Expansion Study of the Anti-PD-1 Monoclonal Antibody CS1003 in Subjects With Advanced Solid Tumors

Conditions
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Advanced Cancer

Intervention / Treatment
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* Biological: CS1003
* Biological: CS1003
* Drug: Regorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have histologically or cytologically confirmed advanced or metastatic solid tumor and have progressed, are intolerant to, refuse to accept or do not have access to standard therapy. ECOG performance status of 0 or 1. Subjects with evaluable but non-measurable lesion are eligible for Phase Ia. Subjects must have at least one measurable lesion per RECIST Version 1.1 to be eligible for Phase Ib. Archived tumor tissue samples need to be collected, or subjects consent to undergo pre-treatment biopsy if archived sample is not available. Life expectancy ≥ 3 months. Subject must have adequate organ function. Use of effective contraception (males and females). Exclusion Criteria: Subjects with known symptomatic or untreated brain metastasis or other CNS metastasis. Subjects with active autoimmune diseases or history of autoimmune diseases. Subjects who have to receive glucocorticoids (prednisone at > 10 mg/day or equivalent) or other immunosuppression within 14 days prior to the first dose of CS1003. Subjects with other malignant tumor(s) in the past 2 years are not eligible for Phase Ib, except for those with basal cell carcinoma, in situ breast cancer and cervical carcinoma in situ who have undergone radical treatment. Subjects who have received any immune checkpoint treatment, including PD-1, PD-L1, etc. Receipt of chemotherapy, targeted therapy, or any other anti-cancer systemic treatment within 2 weeks prior to the first dose of CS1003. Receipt of major surgical procedure or wide field of radiation within 28 days prior to the first dose of CS1003, local radiotherapy within 14 days prior to the first dose of CS1003, or radioactive agents within 56 days before the first dose of CS1003. Receipt of Chinese herbal medicine or Chinese prepared medicine within 7 days prior to the first dose of CS1003. Receipt of live vaccine within 28 days prior to the first dose of CS1003. History of interstitial lung disease or non-infectious pneumonitis, except for those induced by radiation therapies. History of HIV infection. Subjects with active Hepatitis B and C infection (HBV DNA ≥ 1000 cps/mL or 200 IU/mL) requiring therapy. Subjects with active infection of tuberculosis. Subjects with signs or symptoms of any active infection requiring systemic therapy. History of organ transplantation. Unresolved toxicities from prior anti-cancer therapy. History of any irAE of Grade ≥ 3. History of uncontrolled allergic asthma and serious hypersensitive reaction to monoclonal antibodies. History of alcoholism or drugs abuse. Subjects with major cardiovascular diseases. Any condition that, in the opinion of the investigator or sponsor, would jeopardize compliance. For more information regarding trial participation, please contact at cstonera@cstonepharma.com

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CS1003<br> | Biological: CS1003<br>* In the dose escalation part, the dose levels will be escalated following a modified 3+3 dose escalation scheme. In the dose expansion part, patients will be assigned to different groups based on their tumor type.<br>|
| Experimental: CS1003 + regorafenib<br> | Biological: CS1003<br>* CS1003 to be intravenously administered at the dose level determined during the dose escalation part<br>Drug: Regorafenib<br>* Regorafenib to be orally administered at the protocol-specified dose level, once daily for the first 21 days of each 28-day cycle<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 30 days after last dose of CS1003 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time curve (AUC) |  | From the day of first dose to 30 days after last dose of CS1003 | 
| Maximum plasma concentration (Cmax) |  | From the day of first dose to 30 days after last dose of CS1003 | 
| Time to reach maximum plasma concentration (Tmax) |  | From the day of first dose to 30 days after last dose of CS1003 | 
| Terminal elimination half-life (t1/2) |  | From the day of first dose to 30 days after last dose of CS1003 | 
| Disease assessment by CT/MRI scan |  | To be performed every 9 weeks during treatment period (up to 2 years) and within 30 days after last dose of CS1003 | 
| Anti-CS1003 antibody |  | From the day of first dose to 30 days after last dose of CS1003 |