Clinical trial NCT05806099: 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
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Non-Hodgkin's Lymphoma
Lead sponsor: Beijing Mabworks Biotech Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-04-10
Enrollment: 132
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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)


Eligibility criteria: 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.

Primary outcomes:
measure: Phase I：Percentage of Participants with Adverse Events (AEs)
timeFrame: From Baseline up to approximately 13 months
measure: Phase I：Incidence of Dose Limiting Toxicities (DLTs)
timeFrame: From Baseline up to 3 weeks
measure: Phase I：Maximum Tolerated Dose (MTD) of MBS303
timeFrame: From Baseline up to 3 weeks
measure: Phase I：Recommended Phase Ⅱ Dose (RP2D) of MBS303
timeFrame: From Baseline up to 4 years
measure: Phase Ⅱ ：Antitumor activity as measured by the objective response rate (ORR)
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Phase I and Ⅱ ：Pharmacokinetics: AUC
timeFrame: up to approximately 1 year
measure: Phase I and Ⅱ ：Pharmacokinetics: t1/2
timeFrame: up to approximately 1 year
measure: Phase I and Ⅱ ：Pharmacokinetics: CL
timeFrame: up to approximately 1 year
measure: Phase I and Ⅱ ：Pharmacokinetics: Vd
timeFrame: up to approximately 1 year
measure: Phase I and Ⅱ ：Efficacy: Complete Response Rate (CRR) of MBS303 as Assessed Using Standard Criteria for NHL
timeFrame: Up to approximately 2 years
measure: Phase I and Ⅱ ：Efficacy: Duration of Response (DOR) of MBS303 as Assessed Using Standard Criteria for NHL
timeFrame: Up to approximately 2 years
measure: Phase I and Ⅱ ：Efficacy: Progression-Free Survival (PFS) of MBS303 as Assessed Using Standard Criteria for NHL
timeFrame: Up to approximately 2 years
measure: Phase I and Ⅱ ：Efficacy: Overall Survival (OS) of MBS303
timeFrame: Up to approximately 2 years
measure: Phase I and Ⅱ ：Immunogenicity: Anti-Drug Antibodies (ADA) to MBS303
timeFrame: Up to approximately 1 year
measure: Phase I :Efficacy: ORR
timeFrame: Up to approximately 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
Study officials:
References: