An Open-label, Multicenter, First-in-human, Phase I Dose-escalation and Expansion Clinical Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of MRG001 in Patients With CD20-positive Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (NHL)

Shanghai Miracogen Inc.12 sites in 1 country108 target enrollmentJune 25, 2019

ConditionsRelapsed or Refractory B-cell Non-Hodgkin Lymphoma (NHL)

InterventionsMRG001

DrugsMRG001

Overview

Phase: Phase 1
Intervention: MRG001
Conditions: Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (NHL)
Sponsor: Shanghai Miracogen Inc.
Enrollment: 108
Locations: 12
Primary Endpoint: Adverse Events (AEs)
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This study consists of two parts. Phase Ia is a dose escalation study to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of MRG001. Phase Ib is a dose expansion study to assess the preliminary efficacy of MRG001 in patients with CD20-positive relapsed or refractory B-cell NHL at the confirmed RP2D. The safety, tolerability, pharmacokinetic (PK) and immunogenicity of MRG001 will be evaluated in both parts.

Registry

clinicaltrials.gov

Start Date

June 25, 2019

End Date

October 2023

Last Updated

4 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Shanghai Miracogen Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Voluntarily participates in the clinical study; Fully understands and informed of this study, and provides written informed consent; Willing to follow and have the ability to complete all trial procedures.
•Aged 18 to 80 (including 18 and 80), male or female.
•Patients with histopathologically confirmed relapsed/refractory B-cell non-Hodgkin lymphoma.
•Relapsed or refractory disease after standard of care treatment with anti-CD20 antibodies.
•Patients must have at least one measurable lesion without prior local therapy according to Lugano 2014 criteria.
•The score of ECOG for performance status is 0 or
•Patients without severe hematopoietic, liver and kidney dysfunction.
•Expected survival time ≥ 3 months.
•Prior anti-tumor treatment-related AEs (NCI CTCAE v5.0 Criteria) have recovered to ≤ Grade
•Negative blood pregnancy test for women of childbearing potential within 7 days prior to the first dose of study drug. Patients of childbearing potential should agree to use effective contraception from signing the ICF until 3 months after the last dose of study drug.

Exclusion Criteria

•Applicable to Phase Ia: positive hepatitis B surface antigen (HBsAg), or negative HBsAg with a peripheral blood hepatitis B virus DNA copy number greater than the upper limit of normal; positive hepatitis C virus (HCV) antibody and positive HCV RNA at screening. Patients with a history of clinically significant non-viral hepatitis and cirrhosis. Applicable to Phase Ib: positive hepatitis B surface antigen (HBsAg) and/or positive hepatitis B core antibody (HBcAb) at screening, and peripheral blood hepatitis B virus DNA copy number greater than the upper limit of normal; positive hepatitis C virus (HCV) antibody and positive HCV RNA. Patients with a history of clinically significant non-viral hepatitis and cirrhosis (decompensated cirrhosis Child-Pugh class B, C).
•Positive human immunodeficiency virus (HIV) antibody.
•Any active infection requiring systemic therapy occurred within 2 weeks before enrollment.
•Suspected or confirmed central nervous system invasion of NHL.
•Allergic constitution or known hypersensitivity to rituximab or other anti-CD20 monoclonal antibodies and their components, or hypersensitivity to any component of MRG
•Patients with uncontrolled or significant cardiovascular disease.
•History of severe pulmonary disease.
•Received CAR-T therapy within 3 months before enrollment.
•Received blood transfusion within 28days before enrollment, or receiced erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF) and other drugs that may affect hemogram within 14 days before enrollment.
•Current use of potent CYP3A4 inhibitors or inducers.

Arms & Interventions

MRG001

All patients in Phase Ia (dose escalation) and Phase Ib (dose expansion) will be administrated MRG001 on Day 1 of every 3 weeks (21-day cycle).

Intervention: MRG001

Outcomes

Primary Outcomes

Adverse Events (AEs)

Time Frame: Baseline to 90 days after the last dose of study treatment.

Any reaction, side effect, or untoward event that occurs during the course of the clinical trial whether or not the event is considered related to the study drug.

Maximum Tolerated Dose (MTD)

Time Frame: DLT will be evaluated during the first treatment cycle (Day 1-21).

The highest dose confirmed wherein ≤ 1/6 of patients in a treatment cohort experiences a dose-limiting toxicity (DLT) within 21 days after the first dose of study treatment.

Recommended Phase II Dose (RP2D)

Time Frame: Baseline to study completion (up to 15 months).

The dose level of MRG001 recommended for further phase II clinical studies.

Secondary Outcomes

Progression Free Survival (PFS)(Baseline to study completion (up to 15 months))
Immunogenicity(Baseline to 30 days after the last dose of study treatment)
Objective Response Rate (ORR)(Baseline to study completion (up to 15 months))
Overall Survival (OS)(Baseline to study completion (up to 15 months))
PK parameter: Concentration-time curve(Baseline to 90 days after the last dose of study treatment.)
Duration of Response (DoR)(Baseline to study completion (up to 15 months))
Disease Control Rate (DCR)(Baseline to study completion (up to 15 months))