2023-504931-42-00招募中2 期
A Phase 2 Study to Evaluate the Efficacy and Safety of MK-1026 in Participants with Hematologic Malignancies
适应症
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 238
- 试验地点
- 38
- 主要终点
- Part 1: Number of participants experiencing dose-limiting toxicities (DLTs)
研究概览
简要总结
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Part 1: To determine the safety and tolerability and to establish the RP2D of nemtabrutinib.
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Part 2: Cohorts A to C and J (CLL/ SLL): To evaluate the ORR following administration with nemtabrutinib per iwCLL criteria 2018 as assessed by ICR.
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Part 2: Cohorts D to G (RT, MCL, MZL, FL): To evaluate the ORR following administration with nemtabrutinib per the Lugano criteria 2014 as assessed by ICR.
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Part 2: Cohort H (WM): To evaluate the ORR following administration with nemtabrutinib per IWWM 2014 as assessed by ICR.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 within 7 days prior to allocation
- •Part 1 and Part 2 (Cohorts A to C and J) • Has a confirmed diagnosis of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) with o At least 2 lines of prior therapy (Part 1 only) o Part 2 Cohort A: CLL/SLL participants who are relapsed or refractory to prior therapy with a covalent, irreversible Bruton's tyrosine kinase inhibitor (BTKi), and a B-cell lymphoma 2 inhibitor (BCL2i). CLL participants must have received and failed, been intolerant to, or determined by their treating physician to be a poor phosphoinositide 3-kinase inhibitor (PI3Ki) candidate or ineligible for a PI3Ki per local guidelines o Part 2 Cohort B: CLL/SLL participants who are relapsed or refractory following at least 1 line of prior therapy and are BTKi treatment naive o Part 2 Cohort C: CLL/SLL participants with 17p deletion or tumor protein p53 (TP53) mutation who are relapsed or refractory following at least 1 line of prior therapy o Part 2 Cohort J: CLL/SLL participants whose disease relapsed or was refractory to prior therapy with a covalent/irreversible BTKi and BCL2i o Has active disease for CLL/SLL clearly documented to initiate therapy o Has evaluable core or excisional lymph node biopsy for biomarker analysis from an archival or newly obtained biopsy or bone marrow aspirate at Screening (optional for participants enrolling in Part 1)
- •Part 2 (Cohorts D to G) • Has a confirmed diagnosis of and meets the following prior therapy requirements: o Participants with Richter's transformation who are relapsed or refractory following at least 1 line of prior therapy (Cohort D) o Participants with pathologically confirmed mantle-cell lymphoma (MCL), documented by either overexpression of cyclin D1 or t(11;14), who are relapsed or are refractory to chemoimmunotherapy and a covalent irreversible BTKi (Cohort E) o Participants with marginal zone lymphoma (MZL) (including splenic, nodal, and extra nodal MZL) who are relapsed or refractory to chemoimmunotherapy and a covalent irreversible BTKi (Cohort F) o Participants with follicular lymphoma (FL) who are relapsed or refractory to chemoimmunotherapy, immunomodulatory agents (i.e. lenalidomide plus rituximab) (Cohort G)
- •Have measurable disease defined as at least 1 lesion that can be accurately measured in at least 2 dimensions with spiral computed tomography (CT) scan
- •Has a lymph node biopsy for biomarker analysis from an archival or newly obtained biopsy or bone marrow aspirate (Cohort D) at Screening
- •Part 2 (Cohort H): confirmed diagnosis of Waldenström’s macroglobulinemia (WM); participants who are relapsed or refractory to standard therapies for WM including chemoimmunotherapy and a covalent irreversible BTKi Has active disease defined as 1 of the following: systemic symptoms, physical findings, laboratory abnormalities, coexisting disease Has measurable disease, satisfying any of the following: at least 1 lesion that can be accurately measured in at least 2 dimensions with spiral CT scan (minimum measurement must be >15 mm in the longest diameter or >10 mm in the short axis); immunoglobulin M (IgM) ≥450 mg/dL; or bone marrow infiltration of 10% Has fresh bone marrow aspirate or a lymph node biopsy for biomarker analysis at Screening or a lymph node biopsy from an archival
- •Has a life expectancy of at least 3 months, based on the investigator assessment
- •Has the ability to swallow and retain oral medication
- •Participants who are Hepatitis B surface antigen (HBsAg)-positive are eligible if they have received Hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization
- •Participants with history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
- •Has adequate organ function
- •Male participants agree to refrain from donating sperm and agree to either remain abstinent from penile-vaginal intercourse as their preferred and usual lifestyle OR agree to use contraception, during the intervention period and for at least the time required to eliminate the study intervention after last dose of study intervention
- •Female participants assigned female sex at birth who are not pregnant or breastfeeding are eligible to participate if not a participant of childbearing potential (POCBP), or if a POCBP they either use a contraceptive method that is highly effective OR remain abstinent from penile-vaginal intercourse as their preferred and usual lifestyle during the intervention period and for at least to eliminate the study intervention after the last dose of study intervention
- •Participants with human immunodeficiency virus (HIV) are eligible if they meet all of the following: the cluster of differentiation 4+ (CD4) count is >350 cells/uL at screening, the HIV viral load is below the detectable level, are on a stable antiretroviral therapy (ART) regimen for at least 4 weeks prior to study entry, and are compliant with their ART
排除标准
- •Has active HBV/HCV infection (Part 1 and Part 2)
- •Has a history of malignancy ≤3 years before providing documented informed consent. Participants with basal cell carcinoma of skin, squamous cell carcinoma of skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potential curative therapy are not excluded. Participants with low-risk, early-stage prostate cancer (T1-T2a, Gleason score ≤6, and prostate-specific antigen <10 ng/mL) either treated with definitive intent or untreated in active surveillance with stable disease (SD) are not excluded
- •Has active central nervous system (CNS) disease
- •Has an active infection requiring systemic therapy
- •Has received prior systemic anti-cancer therapy within 4 weeks prior to allocation
- •Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
- •Has any clinically significant gastrointestinal abnormalities that might alter absorption
- •History of severe bleeding disorders
结局指标
主要结局
Part 1: Number of participants experiencing dose-limiting toxicities (DLTs)
Part 1: Number of participants experiencing dose-limiting toxicities (DLTs)
Part 1: Number of participants experiencing adverse events (AEs)
Part 1: Number of participants experiencing adverse events (AEs)
Part 1: Number of participants discontinuing study treatment due to AEs
Part 1: Number of participants discontinuing study treatment due to AEs
Part 2: Objective Response Rate (ORR) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria 2018 as assessed by independent central review (ICR)
Part 2: Objective Response Rate (ORR) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria 2018 as assessed by independent central review (ICR)
Part 2: ORR per Lugano criteria 2014 as assessed by ICR
Part 2: ORR per Lugano criteria 2014 as assessed by ICR
Part 2: ORR per International Workshop on Waldenström’s Macroglobulinemia (IWWM) criteria 2014 as assessed by ICR
Part 2: ORR per International Workshop on Waldenström’s Macroglobulinemia (IWWM) criteria 2014 as assessed by ICR
次要结局
- Part 2: DOR per iwCLL criteria 2018 as assessed by ICR
- Part 1: Area Under the Curve (AUC) of nemtabrutinib
- Part 1: Minimum Concentration (Cmin) of nemtabrutinib
- Part 1: Maximum Concentration (Cmax) of nemtabrutinib
- Part 1: ORR per iwCLL criteria 2018 as assessed by ICR
- Part 1: Duration of Response (DOR) per iwCLL criteria 2018 as assessed by ICR
- Part 2: Number of participants experiencing AEs
- Part 2: Number of participants discontinuing study treatment due to AEs
- Part 2: AUC of nemtabrutinib
- Part 2: Cmin of nemtabrutinib
- Part 2: Cmax of nemtabrutinib
- Part 2: DOR per Lugano criteria 2014 as assessed by ICR
- Part 2: DOR per IWWM criteria 2014 as assessed by ICR
研究者
Jing Yang
Scientific
Merck Sharp & Dohme LLC
研究点 (38)
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