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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 280
- 试验地点
- 41
- 主要终点
- Number of Participants Who Discontinue Study Treatment Due to an AE
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: MK-1045 (Biological)
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.
干预措施: MK-1045 (Biological)
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.
干预措施: MK-1045 (Biological)
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.
干预措施: MK-1045 (Biological)
结局指标
主要结局
Number of Participants Who Discontinue Study Treatment Due to an AE
时间窗: 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.
Number of Participants Who Experience an Adverse Event (AE)
时间窗: Up to approximately 49 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.
Arms 2 and 3: Number of Participants Who Experience Dose Limiting Toxicity (DLT)
时间窗: 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, 2, and 4: Objective Response Rate (ORR) per Lugano Response Criteria as assessed by Blinded Independent Central review (BICR)
时间窗: Up to approximately 49 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, 2, and 4, the percentage of participants who experience CR or PR as assessed by BICR will be presented.
次要结局
- 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)
- Trough Concentration (Ctrough) of MK-1045(Pre-dose and at designated time points post-dose up to 12 months)
- Maximum Serum Concentration (Cmax) of MK-1045(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(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(Pre-dose and at designated time points post-dose up to 12 months)
- Arms 1, 2, and 4: Duration of Response (DOR) per Lugano Response Criteria as assessed by BICR(Up to approximately 49 months)
- Arm 3: DOR per Lugano Response Criteria as assessed by Investigator(Up to approximately 49 months)
- Arm 3: ORR per Lugano Response Criteria as assessed by Investigator(Up to approximately 49 months)