Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
MK-1045 · 7 trials · 12 indications
DLT will be defined as any drug-related adverse event (AE) observed during the DLT evaluation period that results in a change to a given dose or a delay in initiating the next dose.
An AE is defined as 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 is defined as 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.
ORR is defined as the percentage of participants with complete response (CR), complete response with an incomplete recovery of the participant's bone marrow (CRi), nodular partial response (nPR), or partial response (PR), per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria 2018 as assessed by blinded independent central review (BICR).
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
DLT will be defined as any drug-related AE observed during the DLT evaluation period that results in a change to a given dose or a delay in initiating the next cycle.
For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) per Lugano response criteria. CR rate is defined as the percentage of participants who experience a CR. The CR rate as assessed by physician investigator will be presented.
PFS is defined as the time from randomization to the first documented disease progression per Lugano response criteria by Blinded Independent Central Review (BICR) 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
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.
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.
OS is the time from randomization to death due to any cause.
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 number of participants who experience an AE will be reported.
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 number of participants who discontinue study treatment due to an AE will be reported.
DLT will be defined as any drug-related AE observed during the DLT evaluation period (up to 28 days) that results in a change to a given dose or a delay in initiating the next treatment.
ORR is defined as the percentage of the participants who had complete response (CR) or partial response (PR) and will be evaluated using computed tomography (CT) and positron emission tomography (PET)-CT. Response will be assessed based on the International Working Group Criteria: Lugano Classification (Cheson et al, Journal of Clinical Oncology, 2014). CR is complete metabolic (no/minimal fluorodeoxyglucose \[FDG\] uptake) and radiologic response (target lesions regress to ≤1.5 cm in longest transverse diameter of a lesion) and no new lesions. PR is partial metabolic (moderate/high FDG uptake) and radiologic response (≥50% decrease in sum of product diameters for multiple lesions of up to 6 target measurable nodes and extranodal sites, no increase in lesions, and spleen regressed by \>50% in length beyond normal). In Arms 1, 2, and 4, the percentage of participants who experience CR or PR as assessed by BICR will be presented.
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
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.
DLT are any of the following drug related (DR) investigator-assessed adverse events: Grade 4 neutropenia that does not recover to Grade ≤ 2 after more than 5 days of supportive care including granulocyte colony-stimulating factor (G-CSF), or ≥ Grade 3 febrile neutropenia; Grade 4 platelet (PLT) decreased, or Grade 3 PLT decreased with bleeding; Grade 4 anemia. Grade 4 non-hematologic toxicity; Grade 3 non-hematologic toxicity that does not recover to Grade ≤ 2 within 3 days after best supportive care (excluding simple laboratory abnormalities without clinical significance as assessed by the investigator). Participants with ≥ Grade 3 tumor lysis syndrome who recover to ≤ Grade 2 within 14 days after optimal supportive therapy will be excluded from the definition of DLT. A DLT was also any other toxic reactions requiring permanent discontinuation of the study intervention.
An SAE refers to an untoward medical occurrence such as death, life-threatening event, permanent or serious disability or loss of function, need for hospitalization or prolongation of hospitalization after the participant receives the intervention, and congenital abnormalities or birth defects. The number of participants who experience a SAE will be reported.
An AE is defined as any untoward medical event that occurs after a participant receives the investigational drug, which may be manifested as symptoms, signs, diseases, or laboratory abnormalities, but may not necessarily have a causal relationship with the study intervention. A DRAE is defined as an AE definitely related, probably related, or possibly related to the study intervention. The number of participants who have experienced a DRAE will be reported.
An AE is defined as any untoward medical event that occurs after a participant receives the study intervention, which may be manifested as symptoms, signs, diseases, or laboratory abnormalities, but may not necessarily have a causal relationship with the study intervention. AEs are graded on a scale from 1-5 with 1=Mild, 2=Moderate, 3=Severe or medically significant but not immediately life-threatening, 4= Life threatening consequences, and 5=Death due to AE. The number of participants who experience an AE of grade 3 or above will be presented.
An AE is defined as any untoward medical event that occurs after a participant receives the study intervention, which may be manifested as symptoms, signs, diseases, or laboratory abnormalities, but may not necessarily have a causal relationship with the study intervention. AEs are graded on a scale from 1-5 with 1=Mild, 2=Moderate, 3=Severe or medically significant but not immediately life-threatening, 4= Life threatening consequences, and 5=Death due to AE. The number of participants who experience an AE in each category of AEs from 1-5 will be presented.
An SAE refers to an untoward medical occurrence such as death, life-threatening event, permanent or serious disability or loss of function, need for hospitalization or prolongation of hospitalization after the participant receives the study intervention, and congenital abnormalities or birth defects. A drug related SAE is defined as an SAE definitely related, probably related, or possibly related to the study intervention. The number of participants who experience a SAE or a serious drug-related AE will be reported.
An AE is defined as any untoward medical event that occurs after a participant receives the study intervention, which may be manifested as symptoms, signs, diseases, or laboratory abnormalities, but may not necessarily have a causal relationship with the study intervention. A drug related AE includes AEs definitely related, probably related, and possibly related to the study intervention. The number of participants who experience a dose modification due to an AE or DRAE will be presented.
An AE is defined as any untoward medical event that occurs after a participant receives the study intervention, which may be manifested as symptoms, signs, diseases, or laboratory abnormalities, but may not necessarily have a causal relationship with the study intervention. A drug related AE includes AEs definitely related, probably related, and possibly related to the study intervention. The number of participants who discontinue the study due to an AE will be presented.
An AE is defined as any untoward medical event that occurs after a participant receives the study intervention, which may be manifested as symptoms, signs, diseases, or laboratory abnormalities, but may not necessarily have a causal relationship with the study intervention. A drug related AE includes AEs definitely related, probably related, and possibly related to the study intervention. The number of participants who died due to an AE or DRAE will be presented.
| Arm | Type | Description |
|---|---|---|
| Part 1: Dose Finding | EXPERIMENTAL | Participants will receive a step-up dosing regimen of MK-1045. During Cycle 1, participants will receive priming dose 1 of 1 mg MK-1045 on Day 1, priming dose 2 of 5 mg MK-1045 on Day 4, intermediate dose of 20 mg MK-1045 on Day 8, and then weekly (QW) target dose of 40-90 mg MK-1045 thereafter for up to approximately 2 years. At the discretion of physician investigator and after Sponsor consultation, participants who receive at least 3, 4-week treatment cycles and achieve a complete response may switch to an every two-weeks (Q2W) dosing regimen. |
| Part 2: Dose Expansion | EXPERIMENTAL | Participants will receive MK-1045 QW at the recommended dose determined in Part 1 for up to approximately 2 years. At the discretion of physician investigator and after Sponsor consultation, participants who receive at least 3, 4-week treatment cycles and achieve a complete response may switch to a Q2W dosing regimen. |
| Part 1: MK-1045 plus Rituximab (or biosimilar) | EXPERIMENTAL | Participants will receive escalating doses of MK-1045 (from 2 mg to 90 mg) once weekly (QW) for up to approximately 12 months. Participants will also receive 375 mg/m\^2 rituximab (or biosimilar) once every 4 weeks (Q4W) for up to approximately 6 months. |
| Part 2: MK-1045 plus Rituximab (or biosimilar) | EXPERIMENTAL | Participants will receive MK-1045 QW at the dose determined in Part 1 for up to approximately 12 months. Participants will also receive 375 mg/m\^2 rituximab (or biosimilar) Q4W for up to approximately 6 months. |
| Part 2: Physician's Choice of Chemotherapy plus Rituximab (or biosimilar) | EXPERIMENTAL | Participants will receive physician's choice of: 90 mg/m\^2 bendamustine on Days 1 and 2 of each 4-week cycle for up to 6 cycles (up to approximately 6 months) plus 375 mg/m\^2 rituximab (or biosimilar) Q4W for up to approximately 6 months OR 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 1.4 mg/m\^2 vincristine on day 1 of each 3-week cycle (Q3W) and 100 mg/m\^2 prednisone (or prednisolone) once daily on days 1 through 5 Q3W for up to 6 cycles (up to approximately 4 months) plus 375 mg/m\^2 rituximab (or biosimilar) Q3W for up to approximately 4 months OR 750 mg/m\^2 cyclophosphamide and 1.4 mg/m\^2 vincristine Q3W and 40 mg/day prednisone (or prednisolone) once daily on days 1 through 5 of each 3-week cycle for up to 6 cycles (up to approximately 4 months) plus 375 mg/m\^2 rituximab (or biosimilar) Q3W for up to approximately 6 months. |
| MK-1045 Dose Regimen A | EXPERIMENTAL | 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. |
| MK-1045 Dose Regimen B | EXPERIMENTAL | 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. |
| Blinatumomab | ACTIVE_COMPARATOR | Participants will receive blinatumomab on days 1, 8, 15, and 22 of each 42-day cycle |
| Arm 1: Follicular Lymphoma (FL) MK-1045 Monotherapy Dose Optimization | EXPERIMENTAL | Participants will receive Dosage A of MK-1045 by Intravenous (IV) infusion for up to approximately 1 year of treatment or until discontinuation. |
| Arm 2: FL MK-1045 Longer Dosing Interval | EXPERIMENTAL | Participants will receive Dosage B of MK-1045 by Intravenous (IV) infusion for up to approximately 1 year of treatment or until discontinuation. |
| Arm 3: FL MK-1045 Subcutaneous Administration | EXPERIMENTAL | Participants will receive Dosage C of MK-1045 by subcutaneous (SC) injection for up to approximately 1 year of treatment or until discontinuation. |
| Arm 4: Diffuse Large B-cell Lymphoma (DLBCL) MK-1045 Monotherapy Dose Optimization | EXPERIMENTAL | Participants will receive Dosage D of MK-1045 by Intravenous (IV) infusion for up to approximately 1 year of treatment or until discontinuation. |
| Part 1 Prime Dose Escalation Panels | EXPERIMENTAL | Participants will receive single intravenous (IV) doses of MK-1045 at varying dose levels. |
| Part 2 Step-up Dose Escalation Panels | EXPERIMENTAL | Participants will receive 3 step up doses of MK-1045 as a prime, step-up and target dose over a 3-week dosing interval. |
| Part 3 Dose Expansion Panels (Optional) | EXPERIMENTAL | Participants will receive 3 step up doses of MK-1045 as a prime, step-up and target dose over a 3-week dosing interval. |
| MK-1045: Dose Escalation Phase- Adult Cohort | EXPERIMENTAL | Adults in the dose escalation phase will receive a target dose level of MK-1045 from 600 μg to 120,000 μg, administered by intravenous (IV) infusion. MK-1045 will be administered once per week, in treatment cycles defined as 4 weeks of MK-1045 treatment. |
| MK-1045 : Dose Escalation Phase- Pediatric Cohort | EXPERIMENTAL | Pediatric participants will receive a target dose level of MK-1045 from 320 μg to 60000 μg, with dosing further based upon weight. MK-1045 will be administered by IV infusion once per week, in treatment cycles defined as 4 weeks of MK-1045 treatment. |
| MK-1045 Fixed Dose | EXPERIMENTAL | Participants will receive MK-1045 via intravenous (IV) infusion on Day 1 of each week for 3 consecutive weeks followed by one week off of each four-week cycle for up to 12 months until discontinuation or death. |
| MK-1045 Step-up Dose | EXPERIMENTAL | Participants will receive MK-1045 via an IV infusion in a step-up dose with priming once a week (Q1W) for a 3-week cycle for up to 12 months until discontinuation or death. |
| Name | Type | Description |
|---|---|---|
| MK-1045 | BIOLOGICAL | Intravenous (IV) infusion |
| Acetaminophen (or similar antipyretic) | DRUG | Oral administration as a premedication |
| Diphenhydramine (or similar antihistamine) | DRUG | Per approved product label as a premedication |
| Dexamethasone | DRUG | IV administration as a premedication |
| Tocilizumab | BIOLOGICAL | IV administration as a rescue medication |
| Tocilizumab biosimilar | BIOLOGICAL | IV administration as a rescue medication |
| Siltuximab | BIOLOGICAL | IV administration as a rescue medication |
| Rituximab | BIOLOGICAL | IV infusion |
| Rituximab biosimilar | BIOLOGICAL | IV infusion |
| Bendamustine | DRUG | IV infusion |
| Cyclophosphamide | DRUG | IV infusion |
| Vincristine | DRUG | IV infusion |
| Prednisone | DRUG | Per approved product label |
| Prednisolone | DRUG | Per approved product label |
| Doxorubicin Hydrochloride | DRUG | IV infusion |
| Blinatumomab | BIOLOGICAL | Intravenous administration |
| Acetaminophen | DRUG | Oral administration as a premedication |
| Diphenhydramine | DRUG | Intravenous administration as a premedication |
| Avtozma | DRUG | Intravenous administration as a rescue medication |
| Tyenne | DRUG | Intravenous administration as a rescue medication |
Inclusion Criteria: * Has histologically confirmed chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) active disease that is relapsed/refractory (r/r) to prior therapy. * Has confirmed CD19-positive disease. * If human immunodeficiency virus (HIV)-positive, has well-controlled HIV ...
MK-1045 is an investigational small molecule being developed for B-cell malignancies including B-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, small lymphocytic lymphoma, follicular lymphoma, and other hematologic malignancies. It is also being studied in systemic lupus erythematosus. MK-1045 is not yet approved and is in clinical development.
MK-1045 targets CD19, a protein expressed on B cells. By binding to CD19, the drug is designed to interfere with B-cell signaling and survival, which is relevant in CD19-positive B-cell cancers and autoimmune conditions. This mechanism is being evaluated in clinical trials for hematologic malignancies.
MK-1045 is being developed by Merck & Company, Inc., which trades under the ticker MRK. The company is conducting clinical trials of MK-1045 across multiple countries, including the United States, China, Japan, and several European nations, for various B-cell malignancies.
MK-1045 is in Phase 1 and Phase 2 clinical trials. The earliest trial is Phase 1, testing the drug in precursor B-cell acute lymphoblastic leukemia. Additional Phase 2 trials are recruiting or planned for B-cell acute lymphoblastic leukemia, follicular lymphoma, and chronic lymphocytic leukemia. MK-1045 remains investigational.
MK-1045 is being studied in several trials. NCT05579132 is a Phase 1 study in precursor B-cell acute lymphoblastic leukemia in China. NCT07570173 is a Phase 2 trial in B-cell acute lymphoblastic leukemia across multiple countries. NCT07634471 tests MK-1045 with rituximab in follicular lymphoma. NCT07709000 is a Phase 2 trial in chronic lymphocytic leukemia and related conditions.
Yes, MK-1045 is also known as CN201, as indicated in the title of the Phase 1 clinical trial NCT05579132. This alternative name may appear in earlier research or publications. Both names refer to the same investigational drug being developed by Merck for B-cell malignancies.