A Phase 2 Study of Mivavotinib in Biomarker-Defined Subgroups of Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 7
- 主要终点
- Safety as measured by type, incidence, severity, seriousness, and study drug-relatedness of adverse events per Common Terminology Criteria for Adverse Events, version 5
研究概览
简要总结
Study CX-659-401 is a multicenter, open-label, phase 2 study of mivavotinib to evaluate the single-agent activity of mivavotinib in patients with relapsed/refractory non-GCB/ABC DLBCL, incorporating ctDNA-based next-generation sequencing (NGS) to identify DLBCL patients harboring MyD88 and/or CD79B mutations within the study. This goal of this strategy is to evaluate its activity both in the cell-of-origin subgroup of non-GCB/ABC DLBCL and in the genetically defined subgroups of MyD88/CD79B-mutated and wild type DLBCL.
详细描述
Approximately 50 patients will be randomized 1:1 to one of two dose/schedule cohorts: one with a continuous dosing schedule (100 mg QD) and one with an induction dosing schedule (120 mg QD x 14 days, then 80 mg QD starting Day 15). Patients will receive treatment with mivavotinib until disease progression, unacceptable toxicity, withdrawal of consent, or death.
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients aged 18 years or older
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
- •Life expectancy of > 3 months
- •Histologically confirmed de novo or transformed non-GCB DLBCL.
- •Relapsed or refractory to ≥ 2 prior lines of chemotherapy based on standard of care
- •Patients should not have failed more than 5 prior lines of therapy
- •Must have [18F]Fluorodeoxyglucose-positron emission tomography (FDG-PET)-avid measurable disease that meets the size criteria per International Working Group (IWG) criteria.
- •Must have recovered from adverse events of prior anti-cancer therapy to severity ≤ Grade
- •Adequate organ function as assessed by laboratory values.
- •If female of childbearing potential, agreement to use protocol specified contraception methods. If male, agreement to use an effective barrier method of contraception.
排除标准
- •DLBCL with central nervous system (CNS) involvement with active brain or leptomeningeal disease
- •Known human immunodeficiency (HIV; testing not required) or HIV-related malignancy
- •Known hepatitis B surface antigen positive or known or active hepatitis C infection
- •Prior autologous stem cell transplant (ASCT) or chimeric antigen receptor T-cell (CAR-T) cell infusion within 90 days of screening
- •Prior allogeneic stem cell transplantation
- •Unstable/inadequate cardiac function
- •Known gastrointestinal (GI) disease or GI procedure that interferes with swallowing/absorption of oral drug
- •Major surgery within 14 days before the first dose of study drug
- •Serious infection (bacterial/fungal/viral) requiring parenteral antibiotic/antiviral therapy for >5 days within 21 days prior to first dose of study drug
- •Treatment with high-dose corticosteroids for anticancer purposes within 7 days before the first dose of mivavotinib.
- •Use of medication known to be inhibitors or inducers of P-glycoprotein (P-gp) and/or Cytochrome P (CYP)3A
- •Female patients who are pregnant, lactating or breastfeeding.
- •Any radiation therapy within 3 weeks prior to first dose of study treatment.
- •Systemic anticancer treatment within 3 weeks before first dose of study treatment
研究组 & 干预措施
Continuous Dosing Schedule
Mivavotinib 100 mg once daily (QD)
干预措施: Mivavotinib (Drug)
Induction Dosing Schedule
Mivavotinib 120 mg QD for 14 days, then 80 mg QD starting Day 15
干预措施: Mivavotinib (Drug)
结局指标
主要结局
Safety as measured by type, incidence, severity, seriousness, and study drug-relatedness of adverse events per Common Terminology Criteria for Adverse Events, version 5
时间窗: Start of treatment up to 21 months
Type, incidence, severity, seriousness, and study drug-relatedness of AEs assessed by CTCAE v5.0
Overall Response Rate (ORR) as assessed by an independent radiology review committee (IRC) according to the 2014 International Working Group (IWG) Lugano Criteria (Cheson, 2014).
时间窗: Start of treatment up to 21 months
Overall response is defined as a complete response (CR) or partial response (PR). ORR is the proportion of participants who have overall responses.
次要结局
- Duration of Response (DOR) Rate as assessed by an IRC according to the 2014 International Working Group (IWG) Lugano Criteria (Cheson, 2014).(Start of treatment up to 21 months)
- Complete Response (CR) Rate as assessed by an IRC according to the 2014 International Working Group (IWG) Lugano Criteria (Cheson, 2014).(Start of treatment to 21 months)
- Progression-Free Survival (PFS) as assessed by an IRC according to the 2014 International Working Group (IWG) Lugano Criteria (Cheson, 2014).(Start of treatment up to 21 months)