A Clinical Trial of MK-1045 in People With B-cell Acute Lymphoblastic Leukemia (MK-1045-005)

A Phase 2/3, Randomized, Open-Label, Comparison Study of MK-1045 Versus Blinatumomab in Participants With Relapsed or Refractory CD19+ B-Cell Acute Lymphoblastic Leukemia (B-ALL)

Researchers are looking for new ways to treat people with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) that is CD19 positive using a medicine called MK-1045. MK-1045 is an immunotherapy, which is a treatment that helps the immune system fight cancer. This trial will compare MK-1045 to a standard immunotherapy called blinatumomab. The goals of this trial are to learn if more people who receive MK-1045 have no cancer cells in their bone marrow compared to people who receive blinatumomab and if people who receive MK-1045 live longer compared to people who receive blinatumomab.

This study has 2 parts: Part 1 is a dose optimization phase of MK-1045. Part 2 is a randomized phase comparing the efficacy and safety of MK-1045 versus blinatumomab and will use the recommended dose of MK-1045 determined in Part 1

Inclusion Criteria:

• Has a confirmed diagnosis of relapsed/refractory (R/R) B-precursor acute lymphoblastic leukemia (ALL) with 5% or more lymphoblasts in the bone marrow
• Has CD19+ disease, confirmed by local flow cytometry and/or immunohistochemistry testing at the time of enrollment
• Has Philadelphia-negative disease, confirmed by testing, at the time of enrollment
• Participants who have AEs due to previous anticancer therapies must have recovered to Grade ≤1 or baseline
• Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)

Exclusion Criteria:

• Has Burkitt's leukemia
• History or presence of clinically relevant central nervous system (CNS) diseases such as epilepsy, hemorrhagic/ischemic stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, and psychosis
• Has active acute graft versus host disease (GvHD) or chronic GvHD. NOTE: Participants who have received CNI for GvHD within 4 weeks before the first dose of study intervention are also excluded
• History of serious cardiovascular and cerebrovascular diseases.
• HIV-infection with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
• Received prior treatment with blinatumomab within 12 weeks for Part 1 and 24 weeks for Part 2 before the first dose of study intervention (individuals known to be refractory or intolerant to blinatumomab are to be excluded). Refractory to blinatumomab is defined as failure to achieve a response after at least 2 cycles of previous blinatumomab treatment
• Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention
• Known additional malignancy that is progressing or has required active treatment within the past 2 years
• Isolated extramedullary disease (EMD)
• Active autoimmune disease unrelated to ALL that has required systemic treatment in the past 2 years or history of autoimmune disease with potential CNS involvement
• Active infection requiring systemic therapy
• Has not adequately recovered from major surgery or have ongoing surgical complications