Autologous Memory-like NK Cell Therapy With BHV-1100 (Formerly KP1237), Low Dose IL-2 in Multiple Myeloma Patients

Study Overview
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Brief Summary
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This is an open-label single center Phase 1a/1b study with the primary objective of establishing the safety and exploring the efficacy of infusing the ex vivo combination product of cytokine induced memory-like (CIML) NK cells plus KP1237 and low dose IL-2 in newly diagnosed MM patients who have minimal residual disease (MRD+) in first remission prior to autologous stem cell transplant (ASCT).

Official Title
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A Phase 1 Study of Autologous Memory-like Natural Killer (NK) Cell Immunotherapy With BHV-1100 (Formerly KP1237) and IVIG Followed by Low Dose IL-2 as Early Post-Autologous Transplant Consolidation in Minimal Residual Disease Positive, Multiple Myeloma (MM) Patients in First or Second Remission

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Combination Product: CIML NK Cells plus KP1237 and low dose IL-2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Had measurable disease according to Standard Diagnostic Criteria at the time of initial Multiple Myeloma diagnosis Meets criteria for symptomatic multiple myeloma at the time of induction chemotherapy Is transplant eligible based on clinician judgement Willing to undergo ASCT in first remission Achieve partial response or better with induction chemotherapy prior to ASCT according to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma Be MRD+ disease upon restaging prior to stem cell collection and ASCT Eastern Cooperative Oncology Group (EGOG) performance status score of less than 2 Life expectancy greater than six months Have no evidence of active or decompensated heart failure, no recent history (past 6 months) acute myocardial infarction, no evidence of severe valvular disease and must have a LVEF over 50% at the time of transplant evaluation Adequate kidney function No evidence of moderate/severe restrictive or obstructive lung disease at the time of transplant evaluation Adequate bone marrow function Be willing to undergo CD34+ cell collection for stem cell transplant Be willing to undergo leukapherisis Adequate hepatic function If of child-bearing potential, be willing to follow birth control and pregnancy testing practice as recommended Be willing to undergo bone marrow aspirate and biopsy as per treatment plan Exclusion Criteria: Prior autologous or allogeneic hematopoietic stem cell transplant Prior cellular therapies, including NK cell therapy Prior treatment with monoclonal antibodies Prior treatment with melphalan Prior treatment with immunosuppressive or immunomodulatory agents within 30 days of enrollment Disease progression at the time of enrollment History of plasma cell leukemia at any time prior to enrollment Patients seropositive for the human immunodeficiency virus (HIV) Uncontrolled, Hepatitis C Virus or Hepatitis B Virus infection Patient receiving other investigational or anti-myeloma drugs within 30 days of enrollment Patients with active clinically significant autoimmune diseases Patients with active, clinically significant cancer other than multiple myeloma Patients with neurological conditions that make difficult the assessment of neurologic toxicity of the Combination Product

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Newly diagnosed multiple myeloma patients<br>Newly diagnosed MM patients who have minimal residual disease (MRD+) in first remission prior to autologous stem cell transplant (ASCT) | Combination Product: CIML NK Cells plus KP1237 and low dose IL-2<br>* Single dose infusion of CIML NK Cells plus KP1237 followed by low dose IL-2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicities following Combination Product dministration |  | 100 days post Combination Product administration | 
| Incidence and severity of side effects related to the Combination Product |  | 100 days post Combination Product administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of MRD conversion from positive to negative |  | 90-100 days post-ASCT | 
| Rate of MRD conversion from positive to negative |  | 1 year post-ASCT | 
| Rate of MRD conversion from positive to negative during the maintenance phase |  | Start of maintenance therapy 90-100 days post ASCT until disease progression (approximately 2-3 years) | 
| Rate of PFS |  | 1 year post Combination Product administration | 
| Rate of OS |  | 1 years post Combination Product administration | 
| Best overall response rate per the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma |  | 90-100 days post-ASCT, 1 year post-ASCT, and overall during maintenance phase (approximately 3 years) | 
| Incidence and severity of cytokine release syndrome per ASBMT consensus grading |  | 100 days post Combination Product administration | 
| Incidence and severity of other Immune-related toxicities by CTCAE version 5.0 |  | 100 days post Combination Product administration | 
| PK of the KP1237 by determining plasma Cmax |  | 4 days post Combination Product administration | 
| PK of the KP1237 by determining plasma Cmin |  | 4 days post Combination Product administration | 
| PK of the KP1237 by determining plasma AUC |  | 4 days post Combination Product administration | 
| PK of the KP1237 by determining plasma t1/2 |  | 4 days post Combination Product administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cell Therapy, CIML NK cell therapy, cytokine induced memory-like natural killer cell therapy, immunotherapy, antibody-dependent cell-mediated cytotoxicity, ADCC, CD38 positive, CD38+, plasma cells, multiple myeloma, hematological malignancies