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

Novatim Immune Therapeutics

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Multiple Myeloma

Treatments: Biological: KQ-2003 CAR T-cells

Study type: Interventional

Funder types: Industry

Identifiers

NCT06223646

KQ-2003-AC101

Details and patient eligibility

About

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

Enrollment: 29 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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29 participants in 4 patient groups

Phase 1: Low dose group

Experimental group

Description:

Infusion of KQ-2003 CAR T-cells by single dose of 1.0×10\^6 CAR-T cells/kg

Treatment:

Biological: KQ-2003 CAR T-cells

Phase 1: Medium dose group

Experimental group

Description:

Infusion of KQ-2003 CAR T-cells by single dose of 2.0×10\^6 CAR-T cells/kg

Treatment:

Biological: KQ-2003 CAR T-cells

Phase 1: High dose group

Experimental group

Description:

Infusion of KQ-2003 CAR T-cells by single dose of 3.0×10\^6 CAR-T cells/kg

Treatment:

Biological: KQ-2003 CAR T-cells

Phase 2a: RP2D

Experimental group

Description:

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.

Treatment:

Biological: KQ-2003 CAR T-cells