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

Sponsor

Biohaven Pharmaceuticals, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04634435

Collaborator

Dana-Farber Cancer Institute (Other)

Enrollment

Location

Arm

56.3

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Combination Product: CIML NK Cells plus KP1237 and low dose IL-2	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

25 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase 1 Study of Autologous Memory-like NK Cell Immunotherapy in Combination With KP1237 and Low Dose IL-2 as Early Post Autologous Transplant Consolidation in Minimal Residual Disease Positive, Newly Diagnosed Multiple Myeloma Patients

Actual Study Start Date :

Oct 21, 2021

Anticipated Primary Completion Date :

Jun 30, 2023

Anticipated Study Completion Date :

Jun 30, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Newly diagnosed multiple myeloma patients 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 Single dose infusion of CIML NK Cells plus KP1237 followed by low dose IL-2

Arm

Intervention/Treatment

Experimental: Newly diagnosed multiple myeloma patients

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

Single dose infusion of CIML NK Cells plus KP1237 followed by low dose IL-2

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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
Non secretory multiple myeloma (defined as normal serum and urine immunofixation and normal serum free light chain assay)
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