A Clinical Study of MK-1045 in People With Non-Hodgkin Lymphoma (MK-1045-008)
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorMerck Sharp & Dohme LLC
About this trial
Researchers are looking for new ways to treat 2 types of non-Hodgkin lymphoma (NHL) called follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). FL is a slow-growing type of NHL. DLBCL is a fast-growing type of NHL. NHL is a cancer in the lymphatic system that causes swollen lymph nodes. The lymphatic system is part of the immune system.
In this study, researchers want to learn if MK-1045 can treat FL and DLBCL. MK-1045 is a study treatment that is an immunotherapy, which helps the immune system fight cancer.
The goals of this study are to learn how safe MK-1045 is and if people tolerate it. Researchers also want to see if FL and DLBCL respond (the cancer gets smaller or goes away) to treatment.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Has disease that has relapsed (disease progression after remission) or is refractory (failure to achieve complete or partial response) to at least 2 prior systemic lines of therapy.
Has a histologically confirmed diagnosis of follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL).
DLBCL participants only: has progressed after or is ineligible for transplant and chimeric antigen receptor T (cell) (CAR-T) therapy.
Has provided tumor tissue sample (archival or newly obtained, if performed per standard of care).
Disqualifiers
Has received a solid organ transplant.
Had or has clinically relevant central nervous system (CNS) diseases.
Has a history of serious cardiovascular or cerebrovascular diseases.
Had prior allogenic stem cell transplantation with acute graft-versus-host-disease (GVHD); has ongoing evidence of chronic GVHD manifesting as skin involvement, diarrhea, or increased serum bilirubin; or requires systemic immunosuppression for GVHD.
Trial design
Design model
Parallel
Treatments tested in this trial
MK-1045
Biological/VaccineIntravenous (IV) Infusion or Subcutaneous (SC) injection
Treatment groups
280 Participants
are divided into 4 treatment groupsGroup A: Arm 1: Follicular Lymphoma (FL) MK-1045 Monotherapy Dose OptimizationExperimental treatment 1 intervention
Group B: Arm 2: FL MK-1045 Longer Dosing IntervalExperimental treatment 1 intervention
Group C: Arm 3: FL MK-1045 Subcutaneous AdministrationExperimental treatment 1 intervention
Group D: Arm 4: Diffuse Large B-cell Lymphoma (DLBCL) MK-1045 Monotherapy Dose OptimizationExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Number of Participants Who Experience an Adverse Event (AE)
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.
Time frame
Up to approximately 49 months2
Number of Participants Who Discontinue Study Treatment Due to an AE
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.
Time frame
Up to approximately 12 months3
Arms 2 and 3: Number of Participants Who Experience Dose Limiting Toxicity (DLT)
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.
Time frame
Up to approximately 28 days4
Arms 1, 2, and 4: Objective Response Rate (ORR) per Lugano Response Criteria as assessed by Blinded Independent Central review (BICR)
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.
Time frame
Up to approximately 49 monthsSecondary outcomes
1
Arms 1, 2, and 4: Duration of Response (DOR) per Lugano Response Criteria as assessed by BICR
For participants who demonstrate a confirmed complete response (CR) or partial response (PR), DOR is defined as the time from CR or PR to documented disease progression or death. Participants are assessed using computed tomography (CT) and positron emission tomography (PET)-CT and response will be evaluated based on the 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 (SPD) 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). DOR as assessed by BICR will be presented for Arms 1, 2, and 4.
Time frame
Up to approximately 49 months2
Arm 3: DOR per Lugano Response Criteria as assessed by Investigator
For participants who demonstrate a confirmed complete response (CR) or partial response (PR), DOR is defined as the time from CR or PR to documented disease progression or death. Participants are assessed using computed tomography (CT) and positron emission tomography (PET)-CT and response will be evaluated based on the 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 (SPD) 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). DOR as assessed by the Investigator will be presented for Arm 3.
Time frame
Up to approximately 49 months3
Area Under the Concentration-time Curve Measured at Steady State (AUCss) of MK-1045
Blood samples will be collected to determine the AUCss of MK-1045 in plasma.
Time frame
Pre-dose and at designated time points post-dose up to 12 months4
Trough Concentration (Ctrough) of MK-1045
Blood samples will be collected to determine the Ctrough of MK-1045 in plasma.
Time frame
Pre-dose and at designated time points post-dose up to 12 monthsSponsors and contacts
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Source ClinicalTrials.gov