A Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy Study of MBS303 in B-Cell NHL

Study Overview
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Brief Summary
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This is a Phase I/Ⅱ, multicenter, open-label, dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics(PD) and efficacy of a novel T-Cell bispecific (TCB), MBS303, administered by intravenous (IV) infusion in participants with relapsed or refractory B-cell NHL. This entry-to-human study consists of 2 parts: a dose escalation part (Phase I) and an expansion part (Phase Ⅱ)

Official Title
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A Phase I/Ⅱ Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of MBS303 in Patients With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma

Conditions
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Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: MBS303


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able and willing to provide written informed consent and to comply with the study protocol. Adult patients, ≥18 years of age; CD20+ B-cell Non-Hodgkin Lymphoma who have relapsed after or failed to respond to at least one prior treatment regimen with an anti-CD20 monoclonal antibody and for whom there is no available therapy expected to improve survival; Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; Life expectancy ≥3 months; Measurable disease, defined as at lease one bi-dimensionally measurable nodal lesion, defined as >1.5 cm in its longest dimension, or at least one bi-dimensionally measureable extranodal lesion, defined as >1.0 cm in its longest dimension Adequate hematologic, hepatic, and renal function. Exclusion Criteria: Chronic lymphoblastic leukemia, Burkitt lymphoma or lymphoplasmacytic lymphom; History of central nervous system (CNS) lymphoma or other CNS disease; Participants with known active infection, including bacterial, viral, parasite, mycobacterial, or other infections (excluding nail bed fungal infections); Surgery, chemotherapy, targeted therapy, immunotherapy, radiation therapy, tumor embolization, or other antitumor therapy within 28 days prior to the first MBS303; Active or suspected autoimmune diseases; Known severe allergic reaction or/and infusion reaction to monoclonal antibody; Evidence of significant, uncontrolled concomitant disease; Major surgery within 28 days prior to the first MBS303 administration or expected to undergo major surgery during the study treatment; History of another invasive malignant tumors in past 3 years; Participant with history of confirmed progressive multifocal leukoencephalopathy (PML); Severe hemorrhagic diseases such as hemophilia A, hemophilia B, vascular hemophilia, or spontaneous bleeding requiring blood transfusion or other medical intervention; Infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C (including HBsAg, HBcAb positive with abnormal HBV DNA or HCV RNA); Pregnant or lactating women; Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual contact during the following time periods related to this study: 1) while participating in the study; 2) for at least 12 months after discontinuation of all study treatments.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MBS303<br> | Drug: MBS303<br>* Phase I: The patients confirming to the eligibility criteria will be assigned to one of the 7 dose groups (0.05/0.15/0.45 mg   1.5/6/60 mg, respectively) based on the sequence of inclusion. Each patient will receive MBS303 as per the schedule specified in the respective arms. Based on the safety data of the previous dose groups, if pretreatment with MIL62 is required after disussion by the sponsor and the investigators, the subject should be given an IV infusion of MIL62 1000 mg single dose on the D-7. Phase Ⅱ: One or two recommended doses will be selected based on the results of Phase I. Each patient will receive one of the two recommended doses MBS303 as step-up doses on D1 (low dose) and D8 (intermediate dose) of C1 and at the target dose on D1 of C2-17 (21-day cycles). Based on the previous safety data, if pretreatment with MIL62 is required after disussion by the sponsor and the investigators, the subjects should be given an IV infusion of MIL62 1000 mg single dose on the D-7<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I：Percentage of Participants with Adverse Events (AEs) | Percentage of Participants with AEs and SAEs Assessed by NCI CTCAE v5.0 | From Baseline up to approximately 13 months | 
| Phase I：Incidence of Dose Limiting Toxicities (DLTs) |  | From Baseline up to 3 weeks | 
| Phase I：Maximum Tolerated Dose (MTD) of MBS303 |  | From Baseline up to 3 weeks | 
| Phase I：Recommended Phase Ⅱ Dose (RP2D) of MBS303 |  | From Baseline up to 4 years | 
| Phase Ⅱ ：Antitumor activity as measured by the objective response rate (ORR) |  | Up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I and Ⅱ ：Pharmacokinetics: AUC | The area under the curve (AUC) of serum concentration of MBS303 after the administration | up to approximately 1 year | 
| Phase I and Ⅱ ：Pharmacokinetics: t1/2 | Half-life (t1/2) of MBS303 after administration | up to approximately 1 year | 
| Phase I and Ⅱ ：Pharmacokinetics: CL | Clearance (CL) of MBS303 after administration | up to approximately 1 year | 
| Phase I and Ⅱ ：Pharmacokinetics: Vd | Volume of distribution (Vd) of MBS303 after administration | up to approximately 1 year | 
| Phase I and Ⅱ ：Efficacy: Complete Response Rate (CRR) of MBS303 as Assessed Using Standard Criteria for NHL |  | Up to approximately 2 years | 
| Phase I and Ⅱ ：Efficacy: Duration of Response (DOR) of MBS303 as Assessed Using Standard Criteria for NHL |  | Up to approximately 2 years | 
| Phase I and Ⅱ ：Efficacy: Progression-Free Survival (PFS) of MBS303 as Assessed Using Standard Criteria for NHL |  | Up to approximately 2 years | 
| Phase I and Ⅱ ：Efficacy: Overall Survival (OS) of MBS303 |  | Up to approximately 2 years | 
| Phase I and Ⅱ ：Immunogenicity: Anti-Drug Antibodies (ADA) to MBS303 |  | Up to approximately 1 year | 
| Phase I :Efficacy: ORR |  | Up to approximately 2 years |