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

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

Participants will receive a lower MK-1045 dose once weekly for up to 13 cycles (two 28-day and eleven 42-day cycles). Participants will have the option to change treatment at the end of Part 1.

Biological: MK-1045 · Drug: Acetaminophen · Drug: Diphenhydramine · Drug: Dexamethasone · Drug: Tocilizumab · Drug: Siltuximab · Drug: Avtozma · Drug: Tyenne

Participants will receive a larger MK-1045 dose once weekly for up to 13 cycles (two 28-day and eleven 42-day cycles). Participants will have the option to change treatment at the end of Part 1.

Biological: MK-1045 · Drug: Acetaminophen · Drug: Diphenhydramine · Drug: Dexamethasone · Drug: Tocilizumab · Drug: Siltuximab · Drug: Avtozma · Drug: Tyenne

Participants will receive blinatumomab on days 1, 8, 15, and 22 of each 42-day cycle

Biological: Blinatumomab · Drug: Dexamethasone · Drug: Tocilizumab · Drug: Siltuximab · Drug: Avtozma · Drug: Tyenne

Intravenous administration

Intravenous administration

Oral administration as a premedication

Intravenous administration as a premedication

Intravenous administration as a premedication

Intravenous administration as a rescue medication

Intravenous administration as a rescue medication

Intravenous administration as a rescue medication

Intravenous administration as a rescue medication

Plazo: 3 treatment cycles (up to approximately 126 days; each cycle is up to 42 days; cycle lengths vary between cycle and arm)

CR is defined as:

• No circulating lymphoblasts
• Extramedullary disease negative
• Trilineage hematopoiesis (TLH) and \<5% leukemic blasts
• Absolute neutrophil count (ANC) ≥1000/μL
• Platelets ≥100,000/μL
• No platelet transfusions in the last 7 days
• No administration of short-acting granulocyte colony-stimulating factor (G-CSF) and long-acting G-CSF in the last 3 and 14 days, respectively

Plazo: 3 treatment cycles (up to approximately 126 days; each cycle is up to 42 days; cycle lengths vary between cycle and arm)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants with at least 1 AE will be presented.

Plazo: 3 treatment cycles (up to approximately 126 days; each cycle is up to 42 days; cycle lengths vary between cycle and arm)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinue study intervention due to an AE will be presented.

Plazo: Up to approximately 7 years

OS is the time from randomization to death due to any cause.

Plazo: Up to approximately 7 years

OS is the time from randomization to death due to any cause.

Plazo: 3 treatment cycles (up to approximately 126 days; each cycle is up to 42 days; cycle lengths vary between cycle and arm)

MRD is defined as no detectable leukemia cells below a threshold of at least 10\^-4.

Plazo: 3 treatment cycles (up to approximately 126 days; each cycle is up to 42 days; cycle lengths vary between cycle and arm)

For participants who demonstrate CR or CRh or CRi, duration of remission is defined as the time from the first documented evidence of CR or CRh or CRi (whichever is earlier) until disease progression, relapse, or death due to any cause, whichever occurs first.

CR is defined as:

• No circulating lymphoblasts
• Extramedullary disease negative
• Trilineage hematopoiesis (TLH) and \<5% leukemic blasts
• Absolute neutrophil count (ANC) ≥1000/μL
• Platelets ≥100,000/μL
• No platelet transfusions in the last 7 days
• No administration of short-acting granulocyte colony-stimulating factor (G-CSF) and long-acting G-CSF in the last 3 and 14 days, respectively

CRh is the same as CR but with less stringent requirements for platelet count (≥50,000/μL) and ANC (≥500/μL).

CRi is the same as CR but without recovery of platelet count or without recovery of ANC (platelets \<100,000/μL and ANC ≥1000/μL or platelets ≥100,000/μL and ANC \<1000/μL.

Plazo: 3 treatment cycles (up to approximately 126 days; each cycle is up to 42 days; cycle lengths vary between cycle and arm)

The percentage of participants who meet either CR or CRh requirements will be presented.

CR is defined as:

• No circulating lymphoblasts
• Extramedullary disease negative
• Trilineage hematopoiesis (TLH) and \<5% leukemic blasts
• Absolute neutrophil count (ANC) ≥1000/μL
• Platelets ≥100,000/μL
• No platelet transfusions in the last 7 days
• No administration of short-acting granulocyte colony-stimulating factor (G-CSF) and long-acting G-CSF in the last 3 and 14 days, respectively

CRh is the same as CR but with less stringent requirements for platelet count (≥50,000/μL) and ANC (≥500/μL).

Plazo: Up to approximately 7 years

For participants who demonstrate CR, duration of remission is defined as the time from the first documented evidence of CR until disease progression, relapse, or death due to any cause, whichever occurs first.

CR is defined as:

• No circulating lymphoblasts
• Extramedullary disease negative
• Trilineage hematopoiesis (TLH) and \<5% leukemic blasts
• Absolute neutrophil count (ANC) ≥1000/μL
• Platelets ≥100,000/μL
• No platelet transfusions in the last 7 days
• No administration of short-acting granulocyte colony-stimulating factor (G-CSF) and long-acting G-CSF in the last 3 and 14 days, respectively

Plazo: Up to approximately 7 years

For participants who demonstrate CR or CRh, duration of remission is defined as the time from the first documented evidence of CR or CRh (whichever is earlier) until disease progression, relapse, or death due to any cause, whichever occurs first.

CR is defined as:

• No circulating lymphoblasts
• Extramedullary disease negative
• Trilineage hematopoiesis (TLH) and \<5% leukemic blasts
• Absolute neutrophil count (ANC) ≥1000/μL
• Platelets ≥100,000/μL
• No platelet transfusions in the last 7 days
• No administration of short-acting granulocyte colony-stimulating factor (G-CSF) and long-acting G-CSF in the last 3 and 14 days, respectively

CRh is the same as CR but with less stringent requirements for platelet count (≥50,000/μL) and ANC (≥500/μL).

Plazo: Up to approximately 7 years

For participants who demonstrate CR or CRh or CRi, duration of remission is defined as the time from the first documented evidence of CR or CRh or CRi (whichever is earlier) until disease progression, relapse, or death due to any cause, whichever occurs first.

CR is defined as:

• No circulating lymphoblasts
• Extramedullary disease negative
• Trilineage hematopoiesis (TLH) and \<5% leukemic blasts
• Absolute neutrophil count (ANC) ≥1000/μL
• Platelets ≥100,000/μL
• No platelet transfusions in the last 7 days
• No administration of short-acting granulocyte colony-stimulating factor (G-CSF) and long-acting G-CSF in the last 3 and 14 days, respectively

CRh is the same as CR but with less stringent requirements for platelet count (≥50,000/μL) and ANC (≥500/μL).

CRi is the same as CR but without recovery of platelet count or without recovery of ANC (platelets \<100,000/μL and ANC ≥1000/μL or platelets ≥100,000/μL and ANC \<1000/μL.

Plazo: Up to approximately 7 years

The time from randomization to the first documented disease progression, relapse, or death due to any cause, whichever occurs first.

Plazo: Up to approximately 7 years

The use of allo-HSCT treatment after randomization.

Plazo: Up to approximately 7 years

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants with at least 1 AE will be presented.

Plazo: Up to approximately 7 years

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinue study intervention due to an AE will be presented.

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)