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

NCT06223646 | Recruiting Phase 1

• 1 other identifier: KQ-2003-AC101
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (14)

• Stringent complete response rate (sCRR)

  Through study completion, an average of 2 years

• Duration of Response (DOR)

  Through study completion, an average of 2 years

• Disease Control Rate (DCR)

  Through study completion, an average of 2 years

• Progression-free Survival (PFS)

  Through study completion, an average of 2 years

• Overall Survival (OS)

  Through study completion, an average of 2 years

Study Arms (4)

Phase 1: Low dose group

EXPERIMENTAL

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

Phase 1: Medium dose group

EXPERIMENTAL

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

Phase 1: High dose group

EXPERIMENTAL

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

Phase 2a: RP2D

EXPERIMENTAL

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

Interventions

KQ-2003 CAR T-cells BIOLOGICAL

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.

Phase 1: High dose group; Phase 1: Low dose group; Phase 1: Medium dose group; Phase 2a: RP2D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Chinese Academy of Medical Sciences & Peking Union Medical College Hospital

Beijing, 100730, China

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Jian Li, M.D.

CONTACT

010-65296114; lijian@pumch.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2023
• First Posted: January 25, 2024
• Study Start: January 11, 2024
• Primary Completion: March 31, 2026
• Study Completion: March 31, 2026
• Last Updated: January 25, 2024

Record last verified: 2024-01

Locations

CN (1)