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)
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
132
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
Beijing Cancer Hospital
Beijing, China
RECRUITINGPhase I:Percentage of Participants with Adverse Events (AEs)
Percentage of Participants with AEs and SAEs Assessed by NCI CTCAE v5.0
Time frame: From Baseline up to approximately 13 months
Phase I:Incidence of Dose Limiting Toxicities (DLTs)
Time frame: From Baseline up to 3 weeks
Phase I:Maximum Tolerated Dose (MTD) of MBS303
Time frame: From Baseline up to 3 weeks
Phase I:Recommended Phase Ⅱ Dose (RP2D) of MBS303
Time frame: From Baseline up to 4 years
Phase Ⅱ :Antitumor activity as measured by the objective response rate (ORR)
Time frame: Up to approximately 2 years
Phase I and Ⅱ :Pharmacokinetics: AUC
The area under the curve (AUC) of serum concentration of MBS303 after the administration
Time frame: up to approximately 1 year
Phase I and Ⅱ :Pharmacokinetics: t1/2
Half-life (t1/2) of MBS303 after administration
Time frame: up to approximately 1 year
Phase I and Ⅱ :Pharmacokinetics: CL
Clearance (CL) of MBS303 after administration
Time frame: up to approximately 1 year
Phase I and Ⅱ :Pharmacokinetics: Vd
Volume of distribution (Vd) of MBS303 after administration
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Time frame: up to approximately 1 year
Phase I and Ⅱ :Efficacy: Complete Response Rate (CRR) of MBS303 as Assessed Using Standard Criteria for NHL
Time frame: Up to approximately 2 years
Phase I and Ⅱ :Efficacy: Duration of Response (DOR) of MBS303 as Assessed Using Standard Criteria for NHL
Time frame: Up to approximately 2 years
Phase I and Ⅱ :Efficacy: Progression-Free Survival (PFS) of MBS303 as Assessed Using Standard Criteria for NHL
Time frame: Up to approximately 2 years
Phase I and Ⅱ :Efficacy: Overall Survival (OS) of MBS303
Time frame: Up to approximately 2 years
Phase I and Ⅱ :Immunogenicity: Anti-Drug Antibodies (ADA) to MBS303
Time frame: Up to approximately 1 year
Phase I :Efficacy: ORR
Time frame: Up to approximately 2 years