A Phase I Study of MSB2311 in Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a phase I study to determine the safety and toxicity, PK/PD, immunogenicity, biomarkers, anti-tumor activity and establish a preliminary recommended Phase 2 dose (RP2D) in subjects with advanced solid tumors.

Detailed Description
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This is a first-in-human (FIH), open-label, Phase 1 dose-Escalation Study of MSB2311, a humanized anti-PD-L1 monoclonal antibody, in subjects with advanced solid tumors. Qualified subjects will be enrolled to receive their assigned dose regimen of MSB2311 until disease progression or intolerable toxicity, withdrawal of consent, or end of study, whichever occurs first. The maximum treatment duration is 2 years. During the study, subjects will be evaluated for safety and toxicity, PK/PD, immunogenicity, biomarkers, and anti-tumor activity of MSB2311.

Official Title
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First-in-human, Open-label, Phase 1 Dose-Escalation Study of MSB2311, A Humanized Anti-PD-L1 Monoclonal Antibody in Subjects With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: 3 mg/kg Q3W MSB2311 Injection
* Drug: 10 mg/kg Q3W MSB2311 Injection
* Drug: 20 mg/kg Q3W MSB2311 Injection
* Drug: 10 mg/kg Q2W MSB2311 Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to understand and willing to sign the ICF. Male or female subject ≥ 18 years. Histologically/cytologically confirmed, locally advanced unresectable or metastatic solid tumors that are refractory to standard therapy, or for which no standard therapy exists. Subject has measurable disease per RECIST v1.1. ECOG Performance Status 0 to 1 Subjects with life expectancy of ≥ 3 month No herbal/alternative medications prior to the first dose Must have adequate hematological, hepatic and renal function as defined in the protocol. Prior anti-tumor therapies of different kinds must have stopped before the first dose as defined by protocol Effective contraception for both male and female subjects if the risk of conception exists Exclusion Criteria: Pregnant or nursing females. Any remaining AEs > grade 1 from prior anti-tumor treatment as per CTCAE v4. 03, with exception of the residual hair loss; Received a biologic G-CSF, GM-CSF or erythropoietin within 14 days prior to the first dose of study drug; Subjects who had prior treatment with an anti-PD-L1 product History of documented autoimmune disease except for autoimmune hypothyroidism and well-controlled Type 1 diabetes mellitus. W/o autoimmune condition requiring systemic treatment with immunosuppressive medications within 14 days before the planned first dose of study drug. Primacy central nervous system (CNS) malignancy or symptomatic CNS metastases are not allowed, with exceptions defined in protocol. Major surgery within the 28-days from the screening Subjects with idiopathic pulmonary fibrosis or unresolved active or chronic inflammatory pulmonary disease are excluded. History of human immunodeficiency virus (HIV) infection, active hepatitis B or C. HBV carriers History of primary immunodeficiency, stem cell or organ transplant, or previous clinical diagnosis of tuberculosis disease. Clinically significant acute infections 4 weeks and any infection 2 weeks prior to the first dose administration. Known allergies, hypersensitivity, or intolerance to protein-based therapies or with a history of any significant drug allergy Subjects who experienced immunotherapy-related adverse events (irAE) grade ≥ 3, or who had to discontinue prior anti-PD-1 treatment due to irAEs of any grade. Severe or uncontrolled cardiac disease requiring treatment as defined in protocol Any other serious underlying medical, psychiatric, psychological, familial or geographical condition that, in the judgment of the investigator, might impair the subject's benefit from the trial treatment Known history of hypersensitivity to any components of the MSB2311 product.

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: Sequential Assignment
Interventional Model Description: Dose escalation : 3mg/kg Q3W, 10 mg/kg Q3W, 20 mg/kg Q3W, 10 mg/kg Q2W
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 3 mg/kg (Q3W) MSB2311 Injection<br>MSB2311 will be administered as an IV infusion once every 3 weeks (Q3W) starting at 3 mg/kg. | Drug: 3 mg/kg Q3W MSB2311 Injection<br>* An intravenous infusion with concentration from 3 mg/kg (Q3W)<br>* Other names: 3 mg/kg Q3W MSB2311;|
| Experimental: 10 mg/kg (Q3W) MSB2311 Injection<br>MSB2311 will be administered as an IV infusion once every 3 weeks (Q3W) starting at 10 mg/kg. | Drug: 10 mg/kg Q3W MSB2311 Injection<br>* An intravenous infusion with concentration from 10 mg/kg (Q3W)<br>* Other names: 10 mg/kg Q3W MSB2311;|
| Experimental: 20 mg/kg (Q3W) MSB2311 Injection<br>MSB2311 will be administered as an IV infusion once every 3 weeks (Q3W) starting at 20 mg/kg. | Drug: 20 mg/kg Q3W MSB2311 Injection<br>* An intravenous infusion with concentration from 20 mg/kg (Q3W)<br>* Other names: 20 mg/kg Q3W MSB2311;|
| Experimental: 10 mg/kg (Q2W) MSB2311 Injection<br>MSB2311 will be administered as an IV infusion once every 2weeks (Q2W) starting at 10 mg/kg. | Drug: 10 mg/kg Q2W MSB2311 Injection<br>* An intravenous infusion with concentration from 10 mg/kg (Q2W)<br>* Other names: 10 mg/kg Q2W MSB2311;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of MSB2311 | Measured by number adverse events that are related to treatment | Up to 90 days following the last dose | 
| Maximum tolerated dose or recommended phase 2 dose | Measured by number of subjects experiencing DLT in each escalation cohort | Up to 90 days following the last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve (AUC) for MSB2311 |  | Up to 30 days following the last dose | 
| Peak Plasma concentration (Cmax)for MSB2311 | Incidence and quantity of anti-drug antibodies | Up to 30 days following the last dose | 
| Volume of plasma from which MSB2311 is completely removed per unit time (CL) |  | Up to 30 days following the last dose | 
| The incidence of subjects generating anti-drug antibody |  | Up to 30 days following the last dose | 
| Objective response rate (ORR) as measured by RESISTv1.1 |  | Up to 30 days following the last dose | 
| Duration of response (DOR) as measured by RESISTv1.1 |  | Up to 30 days following the last dose | 
| Progression-free survival (PFS) as measured by RESISTv1.1 |  | Up to 30 days following the last dose | 
| Best overall response as measured by RESISTv1.1 |  | Up to 30 days following the last dose | 
| Overall survival (OS) as measured by RESISTv1.1 |  | Up to 30 days following the last dose | 
| Elimination half-life and apparent plasma terminal phase elimination rate constant (t1/2 ) of MSB2311 |  | Up to 30 days following the last dose |