A Study of KQ-2003 CAR-T Cell Therapy for Patients With Relapsed or Refractory Multiple Myeloma

A Phase 1/2a Study to Evaluate the Safety, Tolerability, Preliminary Efficacy, and Pharmacokinetic Characterization of KQ-2003 for Patients With Relapsed/Refractory Multiple Myeloma

This is a multicenter, open-label, dose-escalation/expansion phase 1/2a study to evaluate the safety, tolerability, pharmacokinetic/pharmacodynamic characteristics and determine the recommended dose of KQ-2003 CAR T-cells for patients with Relapsed/Refractory Multiple Myeloma

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Biological: KQ-2003 CAR T-cells

• Study Type: Interventional
• Enrollment (Estimated): 29
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jian Li, M.D.; Phone Number: 010-65296114; Email: lijian@pumch.cn

Study Locations

• China
  • Beijing, China, 100730
    • Recruiting
    • Chinese Academy of Medical Sciences & Peking Union Medical College Hospital
    • Contact: Jian Li, M.D.; Phone Number: 01065296114; Email: lijian@pumch.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years old, male or female;
• Diagnosis of MM with relapsed or refractory disease;
• Eastern Cooperative Oncology Group (ECOG) Performance ≤2 ;
• Expected survival of at least 12 weeks;
• Participant has measurable disease;
• Adequate venous access for the apheresis of peripheral blood mononuclear cell;
• Adequate organ function;
• Able and willing to comply with the study protocol and follow-up plan, and sign the informed consent form in writing.

Exclusion Criteria:

• Received any treatment that might influence the activity of CAR-T cells prior to the collection of peripheral blood mononuclear cells;
• Have history of vaccination within the 4 weeks preceding the collection of peripheral blood mononuclear cells;
• Have active bleeding or venous thromboembolic events requiring anticoagulation;
• Have tested positive for cytomegalovirus and/or mycobacterium tuberculosis, or had any uncontrolled active infection within 14 days prior to the collection of peripheral blood mononuclear cells;
• Subjects infected with active HBV or HCV, HIV, syphilis;
• Subjects with known central nervous system disease or multiple myeloma involving the central nervous system (CNS) or presenting with CNS-related symptoms;
• Patients currently experiencing active autoimmune diseases;
• Diagnosed with immunodeficiency or receiving any other form of immunosuppressive therapy within 7 days prior to enrollment in this study.
• Have following severe diseases: unstable angina, cerebrovascular accident or transient ischemic attack, myocardial infarction , New York Heart Association (NYHA) Class ≥ III, congestive heart failure, poorly controlled severe arrhythmias or other cardiac diseases requiring mechanical support; subjects with known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) < 50% of predicted normal; subjects with known moderate or severe persistent asthma, or a history of asthma within the past 2 years, or currently having any category of uncontrolled asthma; subjects requiring oxygen to maintain adequate oxygen saturation; subjects with hypertension whose blood pressure cannot be lowered to the following range despite treatment with two or more antihypertensive medications;.
• Subjects with malignancies other than multiple myeloma;
• Have any non-hematologic toxicity resulting from prior treatments that cannot be restored to ≤ grade 1 or baseline, excluding alopecia and grade 2 neuropathy;
• History of alcohol abuse, drug addiction, substance abuse, or mental illness within the past year;
• Presence of acute graft-versus-host disease (GVHD) or extensive chronic GVHD of Grade ≥ 2 requiring treatment within the 4 weeks before enrollment, or as judged by the investigator to likely require anti-GVHD treatment during the study; Subjects who had previously received BCMA-CD19 dual-target CAR-T cell products or autologous stem cell transplantation within 12 weeks before the collection of peripheral blood mononuclear cells;
• Known allergy or hypersensitivity reactions to cyclophosphamide, fludarabine, dimethyl sulfoxide (DMSO), CD19, or BCMA-targeted drugs;
• Subjects had participated in other clinical trials and used its investigational drugs within the 3 months prior to the collection of peripheral blood mononuclear cells
• Pregnant or lactating women
• Any situation that the investigator believes may increase the risk of subjects or interfere with the results of clinical trials

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1: Low dose group; Infusion of KQ-2003 CAR T-cells by single dose of 1.0×10^6 CAR-T cells/kg	Biological: KQ-2003 CAR T-cells; KQ-2003 CAR T-cell therapy involves autologous chimeric antigen receptor T-cells, capable of targeting both human B cell maturation antigen (anti-BCMA CAR) and CD19 antigen molecules (anti-CD19 CAR) simultaneously as a cellular therapy.
Experimental: Phase 1: Medium dose group; Infusion of KQ-2003 CAR T-cells by single dose of 2.0×10^6 CAR-T cells/kg	Biological: KQ-2003 CAR T-cells; KQ-2003 CAR T-cell therapy involves autologous chimeric antigen receptor T-cells, capable of targeting both human B cell maturation antigen (anti-BCMA CAR) and CD19 antigen molecules (anti-CD19 CAR) simultaneously as a cellular therapy.
Experimental: Phase 1: High dose group; Infusion of KQ-2003 CAR T-cells by single dose of 3.0×10^6 CAR-T cells/kg	Biological: KQ-2003 CAR T-cells; KQ-2003 CAR T-cell therapy involves autologous chimeric antigen receptor T-cells, capable of targeting both human B cell maturation antigen (anti-BCMA CAR) and CD19 antigen molecules (anti-CD19 CAR) simultaneously as a cellular therapy.
Experimental: Phase 2a: RP2D; After all subjects in the Phase 1 dose-escalation study completed DLT observation, RP2D was determined based on the analysis results for the phase 2a expansion study.	Biological: KQ-2003 CAR T-cells; KQ-2003 CAR T-cell therapy involves autologous chimeric antigen receptor T-cells, capable of targeting both human B cell maturation antigen (anti-BCMA CAR) and CD19 antigen molecules (anti-CD19 CAR) simultaneously as a cellular therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with dose-limiting toxicity (DLT)	For DLT evaluation, severity (grade) is classified according to common terminology criteria for adverse events version 5.0 (CTCAE v5.0).	Within 28 days of receiving KQ-2003 CAR T-cells transfusion therapy
Maximum Tolerated Dose (MTD)	At least 6 subjects in the MTD dose group must complete the DLT assessment.	Within 28 days of receiving KQ-2003 CAR T-cells transfusion therapy
Adverse Event	Safety will be assessed by adverse events (AEs), which include clinically significant abnormalities identified during a medical test (e.g. laboratory tests, electrocardiogram, vital signs, physical examinations). AEs will be coded by Medical Dictionary for Regulatory Activities (MedDRA) and their severity will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE, version 5.0).	Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
Recommended Phase 2 Dose (RP2D)	To determine after all subjects in the Phase 1 dose-escalation study completed DLT observation	Through study completion, an average of 1 year
Objective response rate (ORR)	The definition of ORR is the proportion of subjects achieving sCR, CR, VGPR, or PR confirmed by efficacy reassessment after a minimum interval of three months. ORR is calculated as (sCR+CR+VGPR+PR) divided by the total number of cases, multiplied by 100%.	Through study completion, an average of 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stringent complete response rate (sCRR)	The definition of sCRR is the proportion of subjects achieving sCR confirmed by efficacy re-assessment after a minimum interval of three months.	Through study completion, an average of 2 years
Duration of Response (DOR)	DOR will be calculated among responders from the date of initial documentation of a response to the date of first documented evidence of progressive disease.	Through study completion, an average of 2 years
Disease Control Rate (DCR)	The proportion of subjects achieving sCR, CR, VGPR, PR, MR, or disease stability (SD) confirmed by efficacy reassessment after a minimum interval of three months is defined as the DCR.	Through study completion, an average of 2 years
Progression-free Survival (PFS)	The time interval from the first administration of the investigational drug to the first observation of disease progression is calculated, considering the date of entry for patients who died for reasons other than disease progression before progression occurred.	Through study completion, an average of 2 years
Overall Survival (OS)	OS is the time from the start of cell infusion to the death of the subject.	Through study completion, an average of 2 years
Microscopic Residual Disease (MRD) Negativity Rate and Duration	The duration of MRD negativity is the period during which both bone marrow MRD and imaging remain negative.	Through study completion, an average of 2 years
Maximum concentration (Cmax)	Blood and bone marrow samples will be collected and used for pharmacokinetics assessments.	Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
Time to maximum plasma concentration (Tmax)	Blood and bone marrow samples will be collected and used for pharmacokinetics	Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
Levels of IL-6	Blood samples will be collected and used for pharmacodynamic to evaluate the levels about cytokine levels	Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
Levels of IFN-γ	Blood samples will be collected and used for pharmacodynamic to evaluate the levels about cytokine levels	Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
CD4+T lymphocyte count	Blood samples will be collected and used for pharmacodynamic to evaluate the levels about peripheral blood lymphocyte subsets	Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
CD8+T lymphocyte count	Blood samples will be collected and used for pharmacodynamic to evaluate the levels about peripheral blood lymphocyte subsets	Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
ADA	The trial will evaluate the positive rate, titer and duration or persistence of ADA following the administration of CAR T-Cells.	Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
Nab	The trial will evaluate the positive rate, titer and duration or persistence of Nab following the administration of CAR T-Cells.	Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)

Collaborators and Investigators

• Sponsor: Novatim Immune Therapeutics (Zhejiang) Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2024
• Primary Completion (Estimated): March 31, 2026
• Study Completion (Estimated): March 31, 2026

Study Registration Dates

• First Submitted: December 22, 2023
• First Submitted That Met QC Criteria: January 16, 2024
• First Posted (Actual): January 25, 2024

Study Record Updates

• Last Update Posted (Actual): January 25, 2024
• Last Update Submitted That Met QC Criteria: January 16, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: KQ-2003-AC101

Drug and device information, study documents

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