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

Primary Purpose

Non-Hodgkin's Lymphoma

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
MBS303
Sponsored by
Beijing Mabworks Biotech Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Hodgkin's Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Beijing Cancer HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

MBS303

Arm Description

Outcomes

Primary Outcome Measures

Phase I:Percentage of Participants with Adverse Events (AEs)
Percentage of Participants with AEs and SAEs Assessed by NCI CTCAE v5.0
Phase I:Incidence of Dose Limiting Toxicities (DLTs)
Phase I:Maximum Tolerated Dose (MTD) of MBS303
Phase I:Recommended Phase Ⅱ Dose (RP2D) of MBS303
Phase Ⅱ :Antitumor activity as measured by the objective response rate (ORR)

Secondary Outcome Measures

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

Full Information

First Posted
March 23, 2023
Last Updated
August 9, 2023
Sponsor
Beijing Mabworks Biotech Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05806099
Brief Title
A Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy Study of MBS303 in B-Cell NHL
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 28, 2023 (Actual)
Primary Completion Date
November 2024 (Anticipated)
Study Completion Date
November 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Beijing Mabworks Biotech Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Hodgkin's Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
132 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
MBS303
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
MBS303
Intervention Description
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
Primary Outcome Measure Information:
Title
Phase I:Percentage of Participants with Adverse Events (AEs)
Description
Percentage of Participants with AEs and SAEs Assessed by NCI CTCAE v5.0
Time Frame
From Baseline up to approximately 13 months
Title
Phase I:Incidence of Dose Limiting Toxicities (DLTs)
Time Frame
From Baseline up to 3 weeks
Title
Phase I:Maximum Tolerated Dose (MTD) of MBS303
Time Frame
From Baseline up to 3 weeks
Title
Phase I:Recommended Phase Ⅱ Dose (RP2D) of MBS303
Time Frame
From Baseline up to 4 years
Title
Phase Ⅱ :Antitumor activity as measured by the objective response rate (ORR)
Time Frame
Up to approximately 2 years
Secondary Outcome Measure Information:
Title
Phase I and Ⅱ :Pharmacokinetics: AUC
Description
The area under the curve (AUC) of serum concentration of MBS303 after the administration
Time Frame
up to approximately 1 year
Title
Phase I and Ⅱ :Pharmacokinetics: t1/2
Description
Half-life (t1/2) of MBS303 after administration
Time Frame
up to approximately 1 year
Title
Phase I and Ⅱ :Pharmacokinetics: CL
Description
Clearance (CL) of MBS303 after administration
Time Frame
up to approximately 1 year
Title
Phase I and Ⅱ :Pharmacokinetics: Vd
Description
Volume of distribution (Vd) of MBS303 after administration
Time Frame
up to approximately 1 year
Title
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
Title
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
Title
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
Title
Phase I and Ⅱ :Efficacy: Overall Survival (OS) of MBS303
Time Frame
Up to approximately 2 years
Title
Phase I and Ⅱ :Immunogenicity: Anti-Drug Antibodies (ADA) to MBS303
Time Frame
Up to approximately 1 year
Title
Phase I :Efficacy: ORR
Time Frame
Up to approximately 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yuqin Song, Doctor
Phone
8610-88196118
Email
SongYQ_VIP@163.com
Facility Information:
Facility Name
Beijing Cancer Hospital
City
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yuqin Song, Doctor
Phone
8610-88196118
Email
SongYQ_VIP@163.com

12. IPD Sharing Statement

Learn more about this trial

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

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