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

Overview

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)

Interventions

• Drug MBS303
  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

Primary outcome measures

• Phase I：Percentage of Participants with Adverse Events (AEs) [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]

Secondary outcome measures (10)

• Phase I and Ⅱ ：Pharmacokinetics: AUC [Time frame: up to approximately 1 year]
• Phase I and Ⅱ ：Pharmacokinetics: t1/2 [Time frame: up to approximately 1 year]
• Phase I and Ⅱ ：Pharmacokinetics: CL [Time frame: up to approximately 1 year]
• Phase I and Ⅱ ：Pharmacokinetics: Vd [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]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Beijing Cancer Hospital — Beijing

Identifiers

NCT: NCT05806099 · MBS303-CT101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗