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
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Multiple Myeloma
- Sponsor
- Novatim Immune Therapeutics (Zhejiang) Co., Ltd.
- Enrollment
- 29
- Locations
- 1
- Primary Endpoint
- Objective response rate (ORR)
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
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
Investigators
Eligibility Criteria
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;
Outcomes
Primary Outcomes
Objective response rate (ORR)
Time Frame: Through study completion, an average of 2 years
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%.
Number of patients with dose-limiting toxicity (DLT)
Time Frame: Within 28 days of receiving KQ-2003 CAR T-cells transfusion therapy
For DLT evaluation, severity (grade) is classified according to common terminology criteria for adverse events version 5.0 (CTCAE v5.0).
Maximum Tolerated Dose (MTD)
Time Frame: Within 28 days of receiving KQ-2003 CAR T-cells transfusion therapy
At least 6 subjects in the MTD dose group must complete the DLT assessment.
Recommended Phase 2 Dose (RP2D)
Time Frame: Through study completion, an average of 1 year
To determine after all subjects in the Phase 1 dose-escalation study completed DLT observation
Adverse Event
Time Frame: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
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).
Secondary Outcomes
- Progression-free Survival (PFS)(Through study completion, an average of 2 years)
- Time to maximum plasma concentration (Tmax)(Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1))
- ADA(Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1))
- Duration of Response (DOR)(Through study completion, an average of 2 years)
- Stringent complete response rate (sCRR)(Through study completion, an average of 2 years)
- Overall Survival (OS)(Through study completion, an average of 2 years)
- Maximum concentration (Cmax)(Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1))
- Levels of IFN-γ(Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1))
- Disease Control Rate (DCR)(Through study completion, an average of 2 years)
- Microscopic Residual Disease (MRD) Negativity Rate and Duration(Through study completion, an average of 2 years)
- Levels of IL-6(Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1))
- CD8+T lymphocyte count(Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1))
- CD4+T lymphocyte count(Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1))
- Nab(Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1))