This is an open-label, single-arm pilot study evaluating agenT-797, an invariant natural killer T-cell (iNKT) therapy, in combination with routine clinical care blinatumomab in subjects with Philadelphia chromosome-negative, CD19-positive B-cell acute lymphoblastic leukemia (B-ALL), who have experienced disease progression while receiving blinatumomab, become measurable residual disease (MRD)-positive following prior MRD negativity, or have relapsed disease.
The primary objective of this study is to assess safety and tolerability of the first planned dose of agenT-797 in combination with blinatumomab. Secondary objectives include evaluating the efficacy of combination therapy and other predefined secondary endpoints. Up to 13 subjects will be enrolled in this study.
Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
Subject is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee.
Age ≥ 18 years.
Diagnosis of B-cell ALL.
Loss of CD19 expressions.
Participants with active CNS 3 disease (central nervous system leukemia involvement)
Uncontrolled infection
Philadelphia positive disease (9;22 translocation at location of BCR-ABL1 fusion)
Single group
Invariant Natural Killer T Cell Therapy
Biological/VaccineAgenT-797 is an investigational invariant natural killer T (iNKT) cell therapy administered as a single intravenous infusion in combination with blinatumomab.
Number of participants with Grade 3 or higher Treatment Related Adverse Events -CTCAE
Number of participants with Grade 3 or higher Treatment Related Adverse Events based on The NCI Common Terminology Criteria for Adverse Events (CTCAE) will be reported. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Number of participants with Grade 3 or higher Treatment Related Adverse Events - cytokine release syndrome (CRS)
CRS will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) CRS Consensus Grading. Grade 1 - Mild: Fever ≥38\^ o C, No hypotension, No hypoxia, Grade 2 - Moderate: Fever ≥38\^ o C, Hypotension not requiring vasopressors, Hypoxia requiring low-flow nasal cannula (≤6 L/minute) or blow-by, Grade 3 - Severe: Fever ≥ 38\^ o C, Hypotension requiring a vasopressor with or without vasopressin, Hypoxia requiring high-flow nasal cannula (\>6 L/minute), facemask, nonrebreather mask, or Venturi mask, Grade 4 - Life-threatening: Fever ≥38\^oC, Hypotension requiring multiple vasopressors (excluding vasopressin), Hypoxia requiring positive pressure (e.g. Continuous positive airway pressure, BiPAP, intubation, mechanical ventilation), Grade 5 - Death
Number of participants with Grade 3 or higher Treatment Related Adverse Events - Neurological Toxicity (ICANS)
Immune effector cell-associated neurotoxicity syndrome (ICANS) symptoms will be graded according to the criteria outlined in the protocol on a scale from 1 (mild) to 4 (critical). Cytokine release syndrome (CRS) will be graded according to criteria outlined in the protocol on a scale from 1 (mild) to grade 5 (death).
The effectiveness of the combination therapy
The effectiveness of the combination therapy will be evaluated according to disease status at study entry. Among participants with frank hematologic relapse, efficacy will be defined as a reduction in bone marrow leukemic blasts to \<5% after the first cycle of combination therapy. Among participants with measurable residual disease (MRD) without frank relapse, efficacy will be assessed by the proportion of participants achieving MRD negativity by multiparameter flow cytometry and/or demonstrating a decrease in MRD level from baseline. Among participants with extramedullary disease, efficacy will be assessed by the proportion achieving PET negativity after therapy and, where applicable, by changes in physical examination measurements of skin or superficial extramedullary involvement.
Extramedullary disease response
Extramedullary disease response is defined by resolution of Positron Emission Tomography (PET)-detectable disease on Positron Emission Tomography/Computed Tomography (PET/CT) imaging for participants with PET-avid extramedullary disease at baseline, or reduction in the size of skin or other superficial extramedullary lesions based on physical examination.
Change in residual B-cell acute lymphoblastic leukemia (B-ALL)
Change in residual B-cell acute lymphoblastic leukemia (B-ALL) detected by the clonoSEQ assay, measured by immunoglobulin sequence tracking from baseline to follow-up in participants with available diagnostic samples. ClonoSEQ® assay is a laboratory test used to detect and tracking unique leukemia cell DNA sequences.
Event-Free Survival (EFS)
Event-Free Survival (EFS) is defined as the time from treatment initiation to MRD relapse, clinical relapse, disease progression, or death. Participants will be followed for up to 7 months through study assessments and up to 18 months through medical record review.
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UNC Lineberger Comprehensive Cancer Center
Lead sponsor
MiNK Therapeutics
Collaborator
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