NXC-201 (Formerly HBI0101) Multiple Myeloma

Study Overview
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Brief Summary
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It is a phase one study with dose escalation and safety CART in BCMA- Expressing Multiple Myeloma and AL amyloidosis Patients

Detailed Description
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The intention with NXC-201 (formerly HBI0101) CART is to follow the chimeric antigen receptor T-cells (CART) approach, as for approved products, but target the B cell maturation antigen (BCMA) rather than the CD19 antigen targeted by KYMRIAHTM (tisagenlecleucel) and YESCARTATM (axicabtagene ciloleucel). Importantly, successful results from at least three clinical trials of a BCMA targeted CAR T therapy were published (Zhao 2018, Brundo 2018, Raje 2019), with excellent results obtained for relapsed or refractory multiple myeloma (MM) patients, that validate the approach.

Official Title
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A Phase 1 Dose Escalation and Safety Study of NXC-201 (Formerly HBI0101) CART in BCMA-Expressing Multiple Myeloma Patients

Conditions
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Dose Escalation and Safety

Intervention / Treatment
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* Drug: NXC-201 (formerly HBI0101)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years of age Voluntarily signed informed consent form (ICF) Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2 Diagnosis of MM with relapsed or refractory disease and have had at least 3 different prior lines of therapy including proteasome inhibitor, immunomodulatory therapy and at least one antibody therapy. Subjects must have measurable disease, including at least one of the criteria below: Serum M-protein greater or equal to 0.5 g/dL Urine M-protein greater or equal to 200 mg/24 h Serum free light chain (FLC) assay: involved FLC level greater or equal to 5 mg/dL (50 mg/L) provided serum FLC ratio is abnormal A biopsy-proven evaluable plasmacytoma Bone marrow plasma cells > 20% of total bone marrow cells Non secretory patient will be allowed provided they have measurable disease by PET-CT or bone marrow aspiration, as designated. Women of child-bearing potential (WCBP), must have a negative serum pregnancy test prior to treatment. All sexually active WCBP and all sexually active male subjects must agree to use effective methods of birth control throughout the study Recovery to ≤Grade 2 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 3 neuropathy Ability and willingness to adhere to the study visit schedule and all protocol requirements

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Multiple Myeloma and AL amyloidosis Patients
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CART BCMA<br>The dose escalation phase (Part A) will include the following doses of CAR-positive (CAR+) T cells: 150×10^6, 450×10^6, 800×10^6 or 1200 ×10^6 The expansion phase (Part B) will include a dose between 450×10^6 to 800×10^6 CAR-positive (CAR+) T cells | Drug: NXC-201 (formerly HBI0101)<br>* NXC-201 (formerly HBI0101) CART is defined as autologous T cells transduced ex-vivo with anti-BCMA CAR retroviral vector encoding the chimeric antigen receptor (CAR) targeted to human BCMA. The NXC-201 (formerly HBI0101) CART is provided fresh without cryopreservation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of MTD | Part A: Determination of MTD Part B: Confirmation of selected dose tested (at or below MTD) ( safety ) | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The overall survival | according to the IMWG Uniform Response Criteria for Multiple Myeloma | 2 years | 
| The progression-free survival | according to the IMWG Uniform Response Criteria for Multiple Myeloma | 2 years |