A Clinical Trial of MK-1045 in People With B-cell Cancer (MK-1045-006)

Phase 2Not Yet RecruitingNCT07709000

Merck Sharp & Dohme LLC60 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

Chronic Lymphocytic Leukaemia Small Lymphocytic Lymphoma Hematologic Malignancies

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (4)

Shaare Zedek Medical Center ( Site 0801)

Jerusalem, Israel

Haddasah Medical Center ( Site 0800)

Jerusalem, Israel

Sheba Medical Center ( Site 0802)

Ramat Gan, Israel

Sourasky Medical Center ( Site 0804)

Tel Aviv, Israel

Outcomes

Primary Outcomes

Cohort A Part 1: Number of Participants Who Experience Dose-Limiting Toxicity (DLT)

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.

Time frame: Up to approximately 29 days

Cohort A Part 1: Number of Participants Who Experience an AE

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.

Time frame: Up to approximately 27 months

Cohort A Part 1: Number of Participants Who Discontinue Study Treatment Due to an AE

Time frame: Up to approximately 24 months

Cohort A Parts 1 and 2: Objective Response Rate (ORR)

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).

Time frame: Up to approximately 66 months

Secondary Outcomes

Cohort A Part 2: Number of Participants Who Experience an AE

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.

Time frame: Up to approximately 27 months

Cohort A Part 2: Number of Participants Who Discontinue Study Treatment Due to an AE

Time frame: Up to approximately 24 months

Cohort A Parts 1 and 2: Duration of Response (DOR)

For participants who demonstrate a CR, CRi, nPR, or PR per iwCLL Criteria 2018 as assessed by BICR, DOR is defined as the time from the first documented evidence of CR, CRi, nPR, or PR until disease progression or death due to any cause, whichever occurs first.

Time frame: Up to approximately 66 months

Cohort A Parts 1 and 2: Area Under the Curve at Steady State (AUCss) of MK-1045

Blood samples will be collected at designated timepoints to estimate the AUCss of MK-1045.