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

Phase 1

Recruiting

• Conditions: Non-Hodgkin's Lymphoma
• Interventions: Drug: MBS303

• Registration Number: NCT05806099
• Lead Sponsor: Beijing Mabworks Biotech Co., Ltd.

Brief Summary

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)

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-03-23
• Study First Submitted QC: 2023-04-06
• Study First Posted: 2023-04-10
• Study Start: 2023-06-28
• Status Verified: 2024-07
• Last Update Submitted: 2024-11-19
• Last Update Posted: 2024-11-20
• Primary Completion: 2025-11
• Study Completion: 2026-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 132

Inclusion Criteria

1. Able and willing to provide written informed consent and to comply with the study protocol.
2. Adult patients, ≥18 years of age;
3. 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;
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
5. Life expectancy ≥3 months;
6. 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
7. Adequate hematologic, hepatic, and renal function.

Exclusion Criteria

1. Chronic lymphoblastic leukemia, Burkitt lymphoma or lymphoplasmacytic lymphom;
2. History of central nervous system (CNS) lymphoma or other CNS disease;
3. Participants with known active infection, including bacterial, viral, parasite, mycobacterial, or other infections (excluding nail bed fungal infections);
4. Surgery, chemotherapy, targeted therapy, immunotherapy, radiation therapy, tumor embolization, or other antitumor therapy within 28 days prior to the first MBS303;
5. Active or suspected autoimmune diseases;
6. Known severe allergic reaction or/and infusion reaction to monoclonal antibody;
7. Evidence of significant, uncontrolled concomitant disease;
8. Major surgery within 28 days prior to the first MBS303 administration or expected to undergo major surgery during the study treatment;
9. History of another invasive malignant tumors in past 3 years;
10. Participant with history of confirmed progressive multifocal leukoencephalopathy (PML);
11. Severe hemorrhagic diseases such as hemophilia A, hemophilia B, vascular hemophilia, or spontaneous bleeding requiring blood transfusion or other medical intervention;
12. Infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C (including HBsAg, HBcAb positive with abnormal HBV DNA or HCV RNA);
13. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
MBS303	MBS303	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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 :Efficacy: ORR	Up to approximately 2 years
Phase I and Ⅱ ：Pharmacokinetics: AUC	up to approximately 1 year	The area under the curve (AUC) of serum concentration of MBS303 after the administration
Phase I and Ⅱ ：Pharmacokinetics: t1/2	up to approximately 1 year	Half-life (t1/2) of MBS303 after administration
Phase I and Ⅱ ：Pharmacokinetics: CL	up to approximately 1 year	Clearance (CL) of MBS303 after administration
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 ：Pharmacokinetics: Vd	up to approximately 1 year	Volume of distribution (Vd) of MBS303 after administration
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

Trial Locations

Locations (1)

Beijing Cancer Hospital; 🇨🇳 Beijing, China