A Study of MS-553 in Patients With Relapsed or Refractory B-cell Lymphoma

A Phase I/II Study to Evaluate the Safety and Efficacy of the MS-553 in Patients With Relapsed or Refractory B-cell Lymphoma

This is a Phase I/II, single-arm, multicenter, open-label study which is divided into two portions: Phase I is dose escalation portion, in which subjects with relapsed or refractory B-cell lymphoma will be enrolled except malignant lymphoblastic lymphoma (LBL) and Burkitt lymphoma. After the RP2D is identified, Phase II of subjects with relapsed or refractory mantle cell lymphoma who previously received ≥ 2 and ≤ 4 different chemotherapy and/or targeted drug therapy will be enrolled.

Study Overview

• Status: Terminated
• Conditions: Chronic Lymphocytic Leukemia (CLL); Small Lymphocytic Lymphoma (SLL); Mantle Cell Lymphoma (MCL); Diffuse Large B-cell Lymphoma (DLBCL); Follicular Lymphoma (FL); Relapsed or Refractory B-cell Lymphoma; Marginal Zone Lymphoma (MZL)
• Intervention / Treatment: Drug: MS-553

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Beijing Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1) Patients in Phase I study will be enrolled with refractory or relapsed B-cell non-Hodgkin lymphoma.
• 2) Patients enrolled in the phase I study failed two or more lines of treatment regimens; Patients with mantle cell lymphoma should also be patients with contraindications or failure of BTK inhibitor therapy.
• 3) Eastern Cooperative Oncology Group (ECOG) performance status score is 0~2.
• 4) Have life expectancy ≥ 3 months.

• 5) Major organ functions meet the following criteria:

  • In the absence of growth factor support therapy or blood transfusion in the last 14 days: absolute neutrophil count ≥1.5×109/L, hemoglobin ≥80 g/L, platelets ≥75×109/L (no platelet transfusion within 14 days); if accompanied with bone marrow invasion, neutrophils ≥1.0×109/L, platelets ≥50×109/L.
  • Biochemistry: Total bilirubin ≤1.5×ULN or ≤3.0×ULN in Gilbert's syndrome, AST or ALT ≤2.5×ULN, serum creatinine ≤1.5×ULN or calculated creatinine clearance ≥60 mL/min (Cockcroft-Gault formula).
  • Coagulation function: International normalized ratio (INR) and activated partial thrombin time ≤ 1.5 × ULN.

Exclusion Criteria:

• 1) Present or prior history of other malignancies (except cured carcinoma in situ of cervix and basal cell carcinoma of skin), unless there is radical treatment and no evidence of recurrence or metastasis within the last 2 years.
• 2) Lymphomas involved the central nervous system.
• 3) Patients with history of organ transplantation or allogeneic hematopoietic stem cell transplantation; patients who have received autologous hematopoietic stem cell transplantation or CAR-T treatment within the past 3 months,
• 4) Patients who are suitable and ready for autologous stem cell transplantation.
• 5) History of eye surgery or trauma within 3 months before the screening visit, history of serious eye infection or the most recent eye surgery within 4 weeks before the screening visit.
• 6) Has had active and uncontrolled autoimmune hemocytopenia, including autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura.
• 7) Has had uncontrolled or significant cardiovascular diseases, including:
• 8) Women who are lactating or pregnant.
• 9) Women of child-bearing potential who do not agree to have two pregnancy tests prior to first dose (at least one of tests is serum pregnancy test) and the test result shall be negative.
• 10) Male patients who do not agree to the birth control measures.
• 11) Any conditions that in the opinion of the investigator considers inappropriate to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single arm; dose exploration	Drug: MS-553; MS-553 oral tablet BID x 28-days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of dose limiting toxicity (DLT)	First cycle (28 days)
Incidence and severity of adverse events	up to 24 months
To determine the MTD and RP2D of oral MS-553 in patients with BCL	about 8 months

Secondary Outcome Measures

Outcome Measure	Time Frame
overall survival (OS)	up to 24 months
Objective response rate (ORR)	up to 24 months
Duration of response (DOR)	up to 24 months
progression-free survival (PFS)	up to 24 months
time to progression (TTR)	up to 24 months
disease control rate (DCR)	up to 24 months
Pharmacokinetics parameters: Cmax	within the first 2 cycles (56 days)
Pharmacokinetics parameters: Tmax	within the first 2 cycles (56 days)
Pharmacokinetics parameters: T1/2	within the first 2 cycles (56 days)
Pharmacokinetics parameters: AUC0-12	within the first 2 cycles (56 days)
Pharmacokinetics parameters: CL/F	within the first 2 cycles (56 days)

Collaborators and Investigators

• Sponsor: MingSight Pharmaceuticals, Inc
• Collaborators: Shenzhen MingSight Relin Pharmaceutical Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2023
• Primary Completion (Actual): November 28, 2023
• Study Completion (Actual): November 28, 2023

Study Registration Dates

• First Submitted: January 11, 2023
• First Submitted That Met QC Criteria: February 6, 2023
• First Posted (Actual): February 9, 2023

Study Record Updates

• Last Update Posted (Actual): July 18, 2024
• Last Update Submitted That Met QC Criteria: July 16, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Disease Attributes; Hematologic Diseases; Leukemia, Lymphoid; Leukemia; Leukemia, B-Cell; Chronic Disease; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell; Leukemia, Lymphocytic, Chronic, B-Cell
• Other Study ID Numbers: 2020-003-CN

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No