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

Official title

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

Overview

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

• Biological MK-1045
  Intravenous (IV) Infusion or Subcutaneous (SC) injection

Primary outcome measures

• Number of Participants Who Experience an Adverse Event (AE) [Time frame: Up to approximately 49 months]
• Number of Participants Who Discontinue Study Treatment Due to an AE [Time frame: Up to approximately 12 months]
• Arms 2 and 3: Number of Participants Who Experience Dose Limiting Toxicity (DLT) [Time frame: Up to approximately 28 days]
• Arms 1, 2, and 4: Objective Response Rate (ORR) per Lugano Response Criteria as assessed by Blinded Independent Central review (BICR) [Time frame: Up to approximately 49 months]

Secondary outcome measures (8)

• Arms 1, 2, and 4: Duration of Response (DOR) per Lugano Response Criteria as assessed by BICR [Time frame: Up to approximately 49 months]
• Arm 3: DOR per Lugano Response Criteria as assessed by Investigator [Time frame: Up to approximately 49 months]
• Area Under the Concentration-time Curve Measured at Steady State (AUCss) of MK-1045 [Time frame: Pre-dose and at designated time points post-dose up to 12 months]
• Trough Concentration (Ctrough) of MK-1045 [Time frame: Pre-dose and at designated time points post-dose up to 12 months]
• Maximum Serum Concentration (Cmax) of MK-1045 [Time frame: 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 [Time frame: 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 [Time frame: Pre-dose and at designated time points post-dose up to 12 months]
• Arm 3: ORR per Lugano Response Criteria as assessed by Investigator [Time frame: Up to approximately 49 months]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Israel · 5 centers

• Carmel Hospital ( Site 0602) — Haifa
• Shaare Zedek Medical Center ( Site 0603) — Jerusalem
• Haddasah Medical Center ( Site 0600) — Jerusalem
• Sheba Medical Center ( Site 0601) — Ramat Gan
• Sourasky Medical Center. ( Site 0604) — Tel Aviv

Spain · 5 centers

• Institut Català d'Oncologia (ICO) - Badalona ( Site 1103) — Badalona
• Hospital Virgen de la Victoria ( Site 1104) — Málaga
• Hospital Universitari Vall de Hebron ( Site 1102) — Barcelona
• Hospital Universitario Gregorio Maranon ( Site 1101) — Madrid
• Hospital Universitario 12 de Octubre ( Site 1105) — Madrid

Italy · 4 centers

• Istituto Nazionale Tumori IRCCS Fondazione Pascale-SC Ematologia Oncologica ( Site 0700) — Campania
• INOC - Istituto Nazionale Oncologico Candiolo ( Site 0701) — Candiolo
• Istituto Europeo di Oncologia IRCCS ( Site 0702) — Milan
• Fondazione Policlinico Universitario Agostino Gemelli ( Site 0705) — Roma

Turkey (Türkiye) · 4 centers

• Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 1000) — Ankara
• Antalya Egitim ve Arastirma Hastanesi ( Site 1003) — Antalya
• Koç Üniversitesi Hastanesi ( Site 1001) — Istanbul
• Samsun Ondokuz Mayis Universitesi Tip Fakultesi Hastanesi ( Site 1005) — Samsun

Poland · 3 centers

• Pratia MCM Krakow ( Site 0903) — Krakow
• Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworów Układu Chł — Warsaw
• Pratia Onkologia Katowice ( Site 0902) — Katowice

United States · 2 centers

• Colorado Blood Cancer Institute ( Site 7000) — Denver
• SCRI Oncology Partners ( Site 0100) — Nashville

Argentina · 2 centers

• Instituto Alexander Fleming ( Site 1404) — Ciudad Autonoma de Buenos Aires
• Sanatorio Nuestra Senora del Rosario ( Site 1403) — Rosario

United Kingdom · 2 centers

• Derriford Hospital ( Site 1304) — Plymouth
• The Christie NHS Foundation Trust ( Site 1300) — Manchester

Australia · 1 center

• Townsville University Hospital ( Site 0204) — Townsville

China · 1 center

• Beijing Cancer hospital ( Site 1701) — Beijing

South Korea · 1 center

• The Catholic University of Korea, Yeouido St. Mary's Hospital ( Site 0801) — Seoul

Identifiers

NCT: NCT07519772 · 1045-008 · U1111-1324-8720 · 2025-523005-15-00 · MK-1045-008

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗