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

THE QUICK READ

What this study involves

The registry says this study is recruiting. Individual locations may have different availability.

Study type: Interventional
Phase: Phase 2
Age range: 18 years - Not specified
Sex eligible: All sexes
Healthy volunteers: Not accepted
Participants: 60 Estimated

These are starting points, not an eligibility decision. The research team must review the full requirements.

About the research

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.

Who may be able to participate?

The list below is the sponsor’s full registry wording. It can include conditions, prior treatment, test results and other requirements. A match in search does not mean you qualify.

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.

Understand screening

Treatment, groups and participation

The registry may describe treatments and study duration without a complete visit calendar. Ask the study team for the exact schedule, procedures, risks, costs and alternatives. Keep your usual care plan unless your treating clinician tells you otherwise.

Assignment: Not randomized
Masking: Single masked

Part 1: Dose Finding

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.

Biological: MK-1045 · Drug: Acetaminophen (or similar antipyretic) · Drug: Diphenhydramine (or similar antihistamine) · Drug: Dexamethasone · Biological: Tocilizumab · Biological: Tocilizumab biosimilar · Biological: Siltuximab

Part 2: Dose Expansion

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.

Biological: MK-1045 · Drug: Acetaminophen (or similar antipyretic) · Drug: Diphenhydramine (or similar antihistamine) · Drug: Dexamethasone · Biological: Tocilizumab · Biological: Tocilizumab biosimilar · Biological: Siltuximab

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

Prepare your questions

What researchers are measuring

Outcome measures describe what is being studied. They are not proof that a treatment works.

Primary measures

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 measures

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

Time frame: Up to approximately 27 months

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.

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

Time frame: Up to approximately 24 months

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.

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

Time frame: Up to approximately 66 months

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.

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