A Clinical Study of MK-1045 (CN201) in People With Precursor B-cell Acute Lymphoblastic Leukemia (MK-1045-002)

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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

A DLT is defined as any of the following toxicities and judged by the investigator to be related to the study drug:

Hematologic toxic reactions: If thrombocytopenia, leukopenia, and anemia are caused by primary leukemia, they are not considered as DLTs.

Non-Hematologic toxic reactions: Grade 4 non-hematologic toxicity that does not recover to ≤ Grade 2 within 14 days of best supportive therapy. Grade 3 rash, fatigue, fever, or infection will not be classified as DLT; other Grade 3 non-hematologic toxicities that do not recover to ≤ Grade 2 within 14 days of best supportive therapy is considered DLTs.

Others that are considered as DLTs: Other toxicities considered clinically significant by the investigator that result in permanent drug withdrawal.

The MTD will be determined based on the incidence of DLT in each dose level. The dose level for which the DLT rate is closest to the target DLT rate (30%) will be selected as the MTD.

Complete remission is defined as follows:

< 5% blasts in the bone marrow, no circulating lymphoblasts or extramedullary disease, and full recovery of peripheral blood counts: Platelets ≥100×10^9/L, and absolute neutrophil count (ANC) ≥1.0×10^9/L. The number of participants with CR will be presented.

Blood samples will be collected to determine the AUC from time 0 to the last concentration that can be accurately measured of MK-1045

Blood samples will be collected to determine the AUC0-inf of MK-1045.

Blood samples will be collected to determine the AUC from time to 168 hours after the start of infusion of MK-1045

Blood samples will be collected to determine the AUC0 -tau

Blood samples will be collected to determine the maximum serum drug concentration, obtained directly from the measured value of the plasma concentration-time curve

Blood samples will be collected to determine the Tmax of MK-1045

Blood samples will be collected to determine the Ctrough of MK-1045

Blood samples will be collected to determine the t1/2 of MK-1045

Blood samples will be collected to determine the CL of MK-1045

Blood samples will be collected to determine the Vz of MK-1045

Blood samples will be collected to determine the Vss of MK-1045

Blood samples will be collected to determine the MRT of MK-1045

B cell depletion will be determined at each timepoint by comparing absolute B cell numbers (as determined by flow cytometry) with those at baseline

Peripheral circulating T cell activation will be determined at each timepoint by comparing absolute T cell numbers and T cell activation markers with those at baseline

Blood samples collected at designated timepoints will be used to determine the percentage of participants who develop detectable ADAs to MK-1045

Complete remission is defined as follows:

< 5% blasts in the bone marrow, no circulating lymphoblasts or extramedullary disease, and full recovery of peripheral blood counts: Platelets ≥100×10^9/L, and absolute neutrophil count (ANC) ≥1.0×10^9/L.

CRh is defined as meeting all of the following criteria:

Satisfaction of all criteria for CR except partial recovery of peripheral blood counts (platelets ≥ 50 ×10^9/L and ANC ≥ 0.5×10^9/L). The percentage of participants with CR or CRh will be presented.

Complete remission is defined as follows:

< 5% blasts in the bone marrow, no circulating lymphoblasts or extramedullary disease, and full recovery of peripheral blood counts: Platelets ≥100×10^9/L, and absolute neutrophil count (ANC) ≥1.0×10^9/L.

CRh is defined as meeting all of the following criteria:

Satisfaction of all criteria for CR except partial recovery of peripheral blood counts (platelets ≥ 50 ×10^9/L and ANC ≥ 0.5×10^9/L).

CRi is defined as follows:

<5% blasts in the bone marrow, No circulating lymphoblasts or extramedullary disease, and platelets <100×10^9/L and neutrophils ≥1.0×109/L or platelets ≥100 ×109/L and neutrophils <1.0×10^9/L. The percentage of participants with CR, CRh or CRi will be presented.

MRD-negative is defined as less than 0.01% of leukemic cells were detected in bone marrow with a detection sensitivity no less than 10^-4.

TI is defined as no transfusion for a period of at least 1 week (7 days). The percentage of participants having TI will be presented.

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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

Blood samples will be collected to determine the maximum serum drug concentration, obtained directly from the measured value of the plasma concentration-time curve

Blood samples will be collected to determine the Ctrough of MK-1045

B cell depletion will be determined at each timepoint by comparing absolute B cell numbers (as determined by flow cytometry) with those at baseline

Peripheral circulating T cell activation will be determined at each timepoint by comparing absolute T cell numbers and T cell activation markers with those at baseline

Blood samples will be collected to compare peripheral blood cytokine levels at various time points with those at baseline

Blood samples collected at designated timepoints will be used to determine the percentage of participants who develop detectable ADAs to MK-1045

Complete remission is defined as follows:

< 5% blasts in the bone marrow, no circulating lymphoblasts or extramedullary disease, and full recovery of peripheral blood counts: Platelets ≥100×10^9/L, and absolute neutrophil count (ANC) ≥1.0×10^9/L.

CRh is defined as meeting all of the following criteria:

Satisfaction of all criteria for CR except partial recovery of peripheral blood counts (platelets ≥ 50 ×10^9/L and ANC ≥ 0.5×10^9/L). The percentage of participants with CR or CRh will be presented.

CR is defined as follows:

< 5% blasts in the bone marrow, no circulating lymphoblasts or extramedullary disease, and full recovery of peripheral blood counts: Platelets ≥100×10^9/L, and absolute neutrophil count (ANC) ≥1.0×10^9/L.

CRh is defined as meeting all of the following criteria:

Satisfaction of all criteria for CR except partial recovery of peripheral blood counts (platelets ≥ 50 ×10^9/L and ANC ≥ 0.5×10^9/L).

CRi is defined as follows:

<5% blasts in the bone marrow, No circulating lymphoblasts or extramedullary disease, and platelets <100×10^9/L and neutrophils ≥1.0×109/L or platelets ≥100 ×109/L and neutrophils <1.0×10^9/L. The percentage of participants with CR, CRh or CRi will be presented.

MRD-negative is defined as less than 0.01% of leukemic cells were detected in bone marrow with a detection sensitivity no less than 10^-4.

Red Blood Cell and Platelet TI is defined as no transfusion for a period of at least 1 week (7 days). The percentage of participants having TI will be presented.

The number of participants who undergo a HSCT during study participation will be presented.

For participants who demonstrate a CR (defined as < 5% blasts in the bone marrow, no circulating lymphoblasts or extramedullary disease, and full recovery of peripheral blood counts: Platelets ≥100×10^9/L, and absolute neutrophil count (ANC) ≥1.0×10^9/L) , duration of CR is defined as the time from the first documentation of a disease response of CR to the date of the first documented relapse event, or death due to any cause, whichever occurs first

Duration of CR/CRh is defined as the time from the first documentation of a disease response of CR/CRh to the date of the first documented relapse event, or death due to any cause, whichever occurs first. Only participants who demonstrate a CR (defined as < 5% blasts in the bone marrow, no circulating lymphoblasts or extramedullary disease, and full recovery of peripheral blood counts: Platelets ≥100×10^9/L, and absolute neutrophil count (ANC) ≥1.0×10^9/L), or CRh [satisfaction of all criteria for CR except partial recovery of peripheral blood counts (platelets ≥ 50 ×10^9/L and ANC ≥ 0.5×10^9/L)] will be analyzed.

Duration of CR/CRh/CRi is defined as the time from the first documentation of a disease response of CR/CRh/CRi to the date of the first documented relapse event, or death due to any cause, whichever occurs first. Only participants who demonstrate a CR (defined as < 5% blasts in the bone marrow, no circulating lymphoblasts or extramedullary disease, and full recovery of peripheral blood counts: Platelets ≥100×10^9/L, and absolute neutrophil count (ANC) ≥1.0×10^9/L), or CRh [satisfaction of all criteria for CR except partial recovery of peripheral blood counts (platelets ≥ 50 ×10^9/L and ANC ≥ 0.5×10^9/L)], or CRi (<5% blasts in the bone marrow, No circulating lymphoblasts or extramedullary disease, and platelets <100×10^9/L and neutrophils ≥1.0×109/L or platelets ≥100 ×109/L and neutrophils <1.0×10^9/L) will be analyzed.

RFS is defined as the time from the first dose of MK-1045 to the first documented relapse, or death due to any cause (whichever occurs first). In participants who achieve CR, CRh or CRi, relapse is defined as either hematological or extramedullary relapse . Hematological relapse is defined as recurrence of blasts in the blood, or >5% blasts in bone marrow. Extramedullary relapse is defined as recurrence of extramedullary disease after a CR.

OS is the time from date of first study treatment to the date of death due to any reason.