A Clinical Study of MK-1045 in People With Non-Hodgkin Lymphoma (MK-1045-008)

A Phase 1b/2 Study to Evaluate the Safety and Efficacy of MK-1045 Monotherapy or in Combination With Other Anticancer Agents in Participants With Non-Hodgkin Lymphoma

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.

Study Overview

• Status: Recruiting
• Conditions: Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin
• Intervention / Treatment: Biological: MK-1045

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Toll Free Number; Phone Number: 1-888-577-8839; Email: Trialsites@msd.com

Study Locations

• Israel
  • Jerusalem, Israel, 9112001
    • Recruiting
    • Haddasah Medical Center ( Site 0600)
    • Contact: Study Coordinator; Phone Number: +972539101736

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 exclusion criteria include but are not limited to the following:

• 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.
• Is HIV-infected with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
• Has received a live or live-attenuated vaccine within 30 days of randomization.
• Has received prior CAR-T therapy within 3 months before the first dose of the study intervention.
• Has a known additional malignancy that is progressing or required active treatment within the past 2 years.
• Has known active CNS lymphoma or involvement.
• Has active autoimmune disease that required systemic treatment in the past 2 years.
• Has active infection requiring systemic therapy.
• Has a history of severe bleeding disorders.
• Has not recovered from major surgery or has ongoing surgical complications.
• Has diagnosis of primary mediastinal B-cell lymphoma.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Follicular Lymphoma (FL) MK-1045 Monotherapy Dose Optimization; Participants will receive Dosage A of MK-1045 by Intravenous (IV) infusion for up to approximately 1 year of treatment or until discontinuation.	Biological: MK-1045; Intravenous (IV) Infusion or Subcutaneous (SC) injection; Other Names: CN-201
Experimental: Arm 2: FL MK-1045 Longer Dosing Interval; Participants will receive Dosage B of MK-1045 by Intravenous (IV) infusion for up to approximately 1 year of treatment or until discontinuation.	Biological: MK-1045; Intravenous (IV) Infusion or Subcutaneous (SC) injection; Other Names: CN-201
Experimental: Arm 3: FL MK-1045 Subcutaneous Administration; Participants will receive Dosage C of MK-1045 by subcutaneous (SC) injection for up to approximately 1 year of treatment or until discontinuation.	Biological: MK-1045; Intravenous (IV) Infusion or Subcutaneous (SC) injection; Other Names: CN-201
Experimental: Arm 4: Diffuse Large B-cell Lymphoma (DLBCL) MK-1045 Monotherapy Dose Optimization; Participants will receive Dosage D of MK-1045 by Intravenous (IV) infusion for up to approximately 1 year of treatment or until discontinuation.	Biological: MK-1045; Intravenous (IV) Infusion or Subcutaneous (SC) injection; Other Names: CN-201

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to approximately 44 months
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.	Up to approximately 12 months
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.	Up to approximately 28 Days
Arms 1 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 and 4, the percentage of participants who experience CR or PR as assessed by BICR will be presented.	Up to approximately 44 months
Arm 2: ORR per Lugano Response Criteria as assessed by Investigator	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.	Up to approximately 44 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arms 1 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 and 4.	Up to approximately 44 months
Arms 2 and 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 Arms 2 and 3.	Up to approximately 44 months
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.	Pre-dose and at designated time points post-dose up to 12 months
Trough Concentration (Ctrough) of MK-1045	Blood samples will be collected to determine the Ctrough of MK-1045 in plasma.	Pre-dose and at designated time points post-dose up to 12 months
Maximum Serum Concentration (Cmax) of MK-1045	Blood samples will be collected to determine the Cmax of MK-1045 in plasma.	Pre-dose and at designated time points post-dose up to 12 months
Arms 1, 2, and 4: Time to Maximum Serum Concentration (Tmax) of MK-1045	Blood samples will be collected to determine the Tmax of MK-1045 in plasma.	Pre-dose and at designated time points post-dose up to 12 months
Arm 3: Absolute Bioavailability Expressed as a Percentage (F%) of MK-1045	Blood samples will be collected to determine the F% of MK-1045 in plasma.	Pre-dose and at designated time points post-dose up to 12 months
Arm 3: ORR per Lugano Response Criteria as assessed by Investigator	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.	Up to approximately 44 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2026
• Primary Completion (Estimated): January 20, 2030
• Study Completion (Estimated): October 21, 2030

Study Registration Dates

• First Submitted: April 3, 2026
• First Submitted That Met QC Criteria: April 3, 2026
• First Posted (Actual): April 9, 2026

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, B-Cell; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Lymphoma, Follicular
• Other Study ID Numbers: 1045-008; U1111-1324-8720 (Registry Identifier: UTN); 2025-523005-15-00 (Registry Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No