A Phase 2, Open-label, Multicenter Study to Determine the Safety, Tolerability, and Efficacy of MK-1045 in Participants With Hematologic Malignancies
Trial Snapshot
- Phase
- Phase 2
- Status
- Not yet recruiting
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 60
- Locations
- 3
- Primary Endpoint
- Cohort A Part 1: Number of Participants Who Experience Dose-Limiting Toxicity (DLT)
Study Overview
Brief Summary
Researchers are looking for new ways to treat people with B-cell cancers. In this trial, researchers will look at chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). These are blood cancers that affect B-cells in the blood, bone marrow, or lymph nodes.
The goals of this trial are to learn about:
- The safety of MK-1045 and if participants tolerate it. Tolerate means participants will receive trial treatment unless they need to stop treatment due to health problems.
- The number of participants who respond. Respond means the number of cancer cells goes down or signs of cancer go away.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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 on antiretroviral therapy.
- •If hepatitis B surface antigen (HBsAg)-positive, has undetectable hepatitis B virus (HBV) viral load.
- •If has a history of hepatitis C virus (HCV) infection, has undetectable HCV viral load.
Exclusion Criteria
- •Has a history of serious cardiovascular and cerebrovascular diseases.
- •Has a history or presence of central nervous system disease.
- •Is HIV-infected with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
- •Has a diagnosis of immunodeficiency.
- •Has a known additional malignancy that is progressing or required active treatment within the past 2 years.
- •Has active autoimmune disease (not related to underlying leukemia diagnosis) that required systemic treatment in the past 2 years.
- •Has any active acute graft versus host disease (GvHD) or active chronic GvHD requiring systemic treatment.
- •Has active infection requiring systemic therapy.
- •Has not adequately recovered from major surgery or has ongoing surgical complications.
- •Has a diagnosis of Richter Transformation.
Outcomes
Primary Outcomes
Cohort A Part 1: Number of Participants Who Experience Dose-Limiting Toxicity (DLT)
Time Frame: Up to approximately 29 days
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.
Cohort A Part 1: Number of Participants Who Experience an AE
Time Frame: Up to approximately 27 months
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.
Cohort A Part 1: Number of Participants Who Discontinue Study Treatment Due to an AE
Time Frame: Up to approximately 24 months
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.
Cohort A Parts 1 and 2: Objective Response Rate (ORR)
Time Frame: Up to approximately 66 months
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).
Secondary Outcomes
- Cohort A Part 2: Number of Participants Who Experience an AE(Up to approximately 27 months)
- Cohort A Part 2: Number of Participants Who Discontinue Study Treatment Due to an AE(Up to approximately 24 months)
- Cohort A Parts 1 and 2: Duration of Response (DOR)(Up to approximately 66 months)
- Cohort A Parts 1 and 2: Area Under the Curve at Steady State (AUCss) of MK-1045(Predose and at designated time points post-dose (up to approximately 24 months))
- Cohort A Parts 1 and 2: Maximum Concentration (Cmax) of MK-1045(Predose and at designated time points post-dose (up to approximately 24 months))
- Cohort A Parts 1 and 2: Concentration Immediately Before the Next Dose Is Administered (Ctrough) of MK-1045(Predose and at designated time points post-dose (up to approximately 24 months))
- Cohort A Parts 1 and 2: Percentage of Participants Who Develop Antidrug Antibodies (ADA) to MK-1045(Predose and at designated time points post-dose (up to approximately 24 months))
- Cohort A Parts 1 and 2: Percentage of Participants Who Develop MK-1045 Neutralizing Antibodies (NAb)(Predose and at designated time points post-dose (up to approximately 24 months))