A Study of CS1001 in Combination With Regorafenib in Patients With Advanced or Refractory Solid Tumors

Study Overview
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Brief Summary
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This is a multicenter, open-label study of CS1001 in combination with regorafenib in participants with advanced or refractory cancers. There will be a dose escalation portion in allcomersto find a suitable dose of regorafenib for combination use with CS1001. This study will also enroll participants with specific tumor types in the phase II part of the study to assess the efficacy, pharmacokinetics and safety of the combined regimen (RP2D of regorafenib + CS 1001)

Official Title
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A Phase Ib/II, Multicenter Open-label Study of CS1001 in Combination With Regorafenib in Patients With Advanced or Refractory Solid Tumors

Conditions
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Advanced Refractory Solid Tumors

Intervention / Treatment
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* Drug: CS1001
* Drug: Regorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All participants must have unresectable advanced or metastatic tumors that have histologic or cytologic documentation confirmed. Participant must have at least one measurable lesion by CT or MRI per RECIST 1.1; radiographic tumor assessment should be performed within 28 days prior to initiation of study treatment. ECOG performance status score of 0 or 1. Life expectancy ≥ 12 weeks. Fresh or archival tumor tissue must be provided for PD-L1 expression testing in selected cohorts. Adequate organ function Women of childbearing potential (WOCBP) must have a negative serum pregnancy test result. Either Female or male participants must agree to use adequate contraceptive measures from signing informed consent and for 180 days after last investigational product administration, except for a participant with documented surgical sterilization or a postmenopausal female. Any toxic effects of prior anti-cancer therapy or surgical procedures resolved to baseline severity or NCI-CTCAE version 5 Grade 1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion). Subjects with hepatitis B virus (HBV) infection must have HBV DNA < 2000 IU/mL at screening, and requires continue anti-HBV treatment in the study Exclusion Criteria: Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured. 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. Has known central nervous system (CNS) metastases and/or carcinomatous meningitis that is either symptomatic or untreated. Any prior (within 1 year) or current clinically significant ascites as measured by physical examination and that requires active paracentesis for control. Significant history of cardiac disease within 6 months prior to Day 1 of Cycle 1, myocardial infarction within the previous year, or current cardiac ventricular arrhythmias requiring medication, or left ventricular ejection fraction (LVEF) is below 50%. History or evidence of poorly controlled arterial hypertension. Any serious or uncontrolled medical disorder or active infection may increase the risk associated with study participation or dose. Administration of drugs known as strong CYP3A4 inducers or strong CYP3A4 inhibitors and the last dose was given in < 5 half-lives from the first investigational product administration. Any hemorrhage or bleeding event ≥ CTCAE Grade 3 within 28 days prior to the start of study treatment. Other inclusion/exclusion criteria may apply.

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase Ib arm<br>arms 1. Phase Ib: advanced or refractory solid tumors; | Drug: CS1001<br>* One course will last 28 days. CS1001 will be intravenously administered every 4 weeks (Q4W).<br>Drug: Regorafenib<br>* One course will last 28 days. Administration will be orally (p.o.) taken at different dose schemes.<br>* Other names: BAY 73-4506;|
| Experimental: Phase II arm<br>arms 2.Phase II: subjects with tumor of specific types | Drug: CS1001<br>* One course will last 28 days. CS1001 will be intravenously administered every 4 weeks (Q4W).<br>Drug: Regorafenib<br>* One course will last 28 days. Administration will be orally (p.o.) taken at different dose schemes.<br>* Other names: BAY 73-4506;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase Ib (Safety Evaluation): Number of participants with adverse events |  | Baseline up to 90 days post last dose, up to 2 years | 
| Phase Ib (Safety Evaluation): Dose Limiting Toxicity (DLT) |  | Baseline up to 90 days post last dose, up to 2 years | 
| Phase II (Efficacy Expansion): Objective response rate (ORR) |  | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase Ib (Safety Evaluation): Objective response rate (ORR) |  | Up to 2 years | 
| Phase Ib (Safety Evaluation) and/or Phase II (Efficacy Expansion): Disease control rate (DCR) |  | Up to 2 years | 
| Phase Ib (Safety Evaluation) and/or Phase II (Efficacy Expansion): Progression Free Survival (PFS) |  | Up to 2 years | 
| Phase Ib (Safety Evaluation) and/or Phase II (Efficacy Expansion): Duration of Response (DoR) |  | Up to 2 years | 
| Phase Ib (Safety Evaluation) and/or Phase II (Efficacy Expansion): Overall Survival (OS) |  | Up to 2 years | 
| Phase Ib (Safety Evaluation) and/or Phase II (Efficacy Expansion): Occurrence of anti-CS1001 antibody |  | From first dose to 30 days after last dose, up to 2 years | 
| Phase II (Efficacy Expansion): : Number of participants with adverse events |  | Baseline up to 90 days post last dose, up to 2 years | 
| Phase Ib (Safety Evaluation) and/or Phase II (Efficacy Expansion): Area under the plasma concentration-time curve (AUC)0-t of CS1001 |  | From first dose to 30 days after last dose, up to 2 years | 
| Phase Ib (Safety Evaluation) and/or Phase II (Efficacy Expansion): Maximum plasma concentration (Cmax) of CS1001 |  | From first dose to 30 days after last dose, up to 2 years | 
| Phase Ib (Safety Evaluation) and/or Phase II (Efficacy Expansion): Time to reach maximum plasma concentration (Tmax) of CS1001 |  | From first dose to 30 days after last dose, up to 2 years | 
| Phase Ib (Safety Evaluation) and/or Phase II (Efficacy Expansion): Terminal elimination half-life (t1/2) of CS1001 |  | From first dose to 30 days after last dose, up to 2 years | 
| Phase Ib (Safety Evaluation) and/or Phase II (Efficacy Expansion): Clearance at Steady State (CLss) of CS1001 |  | From first dose to 30 days after last dose, up to 2 years | 
| Phase Ib (Safety Evaluation): Maximum plasma concentration (Cmax) of regorafenib |  | From first dose to 30 days after last dose, up to 2 years | 
| Phase Ib (Safety Evaluation): Minimum plasma concentration (Cmin) of regorafenib |  | From first dose to 30 days after last dose, up to 2 years |