Lymphoma, Follicular, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin
Conditions
Brief summary
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.
Interventions
BIOLOGICALMK-1045
Intravenous (IV) Infusion or Subcutaneous (SC) injection
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The main inclusion criteria include but are not limited to the following: * 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). * Has documented retained expression of cluster of differentiation 19 (CD19) in tumor tissue obtained by biopsy after disease progression on CD19-targeting therapy, if experienced disease progression after prior CD19-targeting therapy. * Has well-controlled human immunodeficiency virus (HIV) on antiretroviral therapy if has a history of HIV infection. * Has undetectable hepatitis B virus (HBV) viral load and received and will continue to receive HBV antiviral therapy if hepatitis B surface antigen (HBsAg)-positive. * Has undetectable hepatitis C virus (HCV) viral load and received HCV antiviral therapy if has a history of HCV infection. * Has radiographically measurable disease per Lugano Response Criteria.
Exclusion criteria
The main
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experience an Adverse Event (AE) | Up to approximately 44 months | 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. |
| Number of Participants Who Discontinue Study Treatment Due to an AE | Up to approximately 12 months | 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. |
| Arms 2 and 3: Number of Participants Who Experience Dose Limiting Toxicity (DLT) | Up to approximately 28 Days | 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. |
| Arms 1 and 4: Objective Response Rate (ORR) per Lugano Response Criteria as assessed by Blinded Independent Central review (BICR) | Up to approximately 44 months | 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 and 4, the percentage of participants who experience CR or PR as assessed by BICR will be presented. |
| Arm 2: ORR per Lugano Response Criteria as assessed by Investigator | Up to approximately 44 months | 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 Arm 2, the percentage of participants who experience CR or PR as assessed by the Investigator will be presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Arms 1 and 4: Duration of Response (DOR) per Lugano Response Criteria as assessed by BICR | Up to approximately 44 months | 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 and 4. |
| Arms 2 and 3: DOR per Lugano Response Criteria as assessed by Investigator | Up to approximately 44 months | 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 Arms 2 and 3. |
| Area Under the Concentration-time Curve Measured at Steady State (AUCss) of MK-1045 | Pre-dose and at designated time points post-dose up to 12 months | Blood samples will be collected to determine the AUCss of MK-1045 in plasma. |
| Trough Concentration (Ctrough) of MK-1045 | Pre-dose and at designated time points post-dose up to 12 months | Blood samples will be collected to determine the Ctrough of MK-1045 in plasma. |
| Maximum Serum Concentration (Cmax) of MK-1045 | Pre-dose and at designated time points post-dose up to 12 months | Blood samples will be collected to determine the Cmax of MK-1045 in plasma. |
| Arms 1, 2, and 4: Time to Maximum Serum Concentration (Tmax) of MK-1045 | Pre-dose and at designated time points post-dose up to 12 months | Blood samples will be collected to determine the Tmax of MK-1045 in plasma. |
| Arm 3: Absolute Bioavailability Expressed as a Percentage (F%) of MK-1045 | Pre-dose and at designated time points post-dose up to 12 months | Blood samples will be collected to determine the F% of MK-1045 in plasma. |
| Arm 3: ORR per Lugano Response Criteria as assessed by Investigator | Up to approximately 44 months | 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 Arm 3, the percentage of participants who experience CR or PR as assessed by the Investigator will be presented. |
Countries
Argentina, China, Israel, Italy, Poland, Spain, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTToll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed