A Phase 1 First in Human Study of ARV-393 in Adult Participants With Advanced Non-Hodgkin's Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Arvinas Inc.
- 入组人数
- 329
- 试验地点
- 21
- 主要终点
- Incidence of Dose Limiting Toxicities During First 28 Days
研究概览
简要总结
This clinical trial is studying the safety and potential anti-tumor activity of an investigational drug called ARV-393 in patients diagnosed with advanced Relapsed/Refractory non-Hodgkin's lymphoma (R/R NHL) to determine if ARV-393 may be a possible treatment option.
ARV-393 is thought to work by breaking down a protein present in many types of non-Hodgkins lymphomas, which may prevent, slow or stop tumor growth. This is the first time ARV-393 will be used by people. The investigational drug will be given as an oral tablet.
详细描述
This is an open-label, global, multi-center monotherapy and combination dose escalation and dose optimization study to evaluate safety, tolerability and preliminary efficacy of ARV-393. The study will evaluate the safety and tolerability in ascending doses of ARV-393 as monotherapy (A) and in combination with glofitamab (C), as well as determine the RP2D in the dose optimization parts (B for monotherapy) and in combination with glofitamab (D for combination therapy). The monotherapy portions of the study will include participants with R/R NHL. The combination therapy portions of the study with glofitamab will include participants with R/R DLBCL.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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
- •For Part A and B: Have relapsed/refractory NHL and >=2 prior systemic therapies, (including rituximab), and be ineligible for known therapies with demonstrated clinical benefit per investigator assessment or, histologically confirmed AITL that has recurred or progressed following institutional standard of care therapy.
- •For Part C and D: Have R/R DLBCL, not otherwise specified [NOS (DLBCL, NOS)] or large B-cell lymphoma (LBCL) arising from follicular lymphoma and have received two or more lines of systemic therapy.
- •Have at least one bi dimensionally measurable lesion >1.5-centimeter (cm) in largest dimension for nodal or >1.0 cm for extranodal lesion.
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 (NOTE: For Part A only - ECOG PS of 2 is allowed for participants with secondary CNS lymphoma).
- •Adequate bone marrow function
- •Adequate kidney function
- •Adequate Liver Function
排除标准
- •Current or past history of peripheral eosinophilia, hypereosinophilic syndrome (HES), organ-specific eosinophilic disorder, or drug reaction with eosinophilia and systemic symptoms (DRESS), except for peripheral eosinophilia due to disease under study. Participants with current or prior eosinophilia requiring systemic steroid treatment are excluded regardless of etiology.
- •Prior allogeneic stem cell transplant (SCT) or solid organ transplantation.
- •Prior treatment with chimeric antigen receptor (CAR) T-cell therapy within 60 days prior to Cycle 1 Day 1 (C1D1) or any prior treatment with a BCL6-targeted therapy
- •Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, melanoma in situ or carcinoma in situ of the breast or cervix, and prostate cancer with active surveillance.
- •Any of the following in the previous 6 months:
- •Myocardial infarction, long QT syndrome or family history of long QT syndrome, or Torsade de Pointes;
- •Clinically important atrial or ventricular arrhythmias;
- •Serious conduction system abnormalities, 3rd degree atrioventricular (AV block), unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (CHF), New York Heart Association Class III or IV;
- •Cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism, and/or other clinically significant episode of thromboembolic disease;
- •Active inflammatory gastrointestinal (GI) disease, chronic diarrhea, previous gastric resection, or lap band surgery.
- •Uncontrolled hypertension despite optimal medical treatment
- •History of myocarditis.
- •In ability to comply with listed prohibited treatments.
- •Standard 12-lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.
- •Cardiac ejection fraction <45%.
研究组 & 干预措施
Part C Combination therapy: Dose escalation
Participants with R/R diffuse large B-cell lymphoma (DLBCL) will receive ARV-393 in combination with glofitamab, beginning at an ARV-393 dose informed by the Part A. Glofitamab will be given per labelled prescribing information. Part C will be conducted in non-USA centers.
干预措施: Glofitamab (Drug)
Part C Combination therapy: Dose escalation
Participants with R/R diffuse large B-cell lymphoma (DLBCL) will receive ARV-393 in combination with glofitamab, beginning at an ARV-393 dose informed by the Part A. Glofitamab will be given per labelled prescribing information. Part C will be conducted in non-USA centers.
干预措施: ARV-393 (Drug)
Part A Monotherapy Dose escalation
Participants with R/R NHL will receive ARV-393 dose escalation beginning at dose level 1
干预措施: ARV-393 (Drug)
Part B Monotherapy: Dose expansion/optimization
Dose expansion and optimization of ARV-393 will be conducted in Part B to determine the recommended phase 2 dose (RP2D) for participants with R/R NHL
干预措施: ARV-393 (Drug)
Part D Combination therapy: Dose expansion/optimization
Part D will be an optimization of ARV-393 in combination with glofitamab to determine a potential RP2D for ARV-393 in the combination regimen. Part D will be conducted in non-USA centers in participants with R/R DLBCL.
干预措施: ARV-393 (Drug)
Part D Combination therapy: Dose expansion/optimization
Part D will be an optimization of ARV-393 in combination with glofitamab to determine a potential RP2D for ARV-393 in the combination regimen. Part D will be conducted in non-USA centers in participants with R/R DLBCL.
干预措施: Glofitamab (Drug)
结局指标
主要结局
Incidence of Dose Limiting Toxicities During First 28 Days
时间窗: 28 days from first study dosing
Percentage of participants in dose escalation arm at a given dose cohort with AEs meeting protocol defined dose limiting toxicities during cycle 1 (28 days)
Percentage of Participants With Adverse Events Characterized by Severity, Seriousness, and Relationship to Study Drug as a Measure of Safety and Tolerability
时间窗: Parts A and B: From the study baseline to 30 days after last dose of ARV-393; Parts C and D: From the study baseline to 40 days after last dose of ARV-393
Adverse events as characterized by type, frequency, severity, seriousness, and relationship to study drug
Number of Participants With Abnormal Vital Signs, Abnormal ECG Readings (QT Interval) and Abnormal Laboratory Parameters
时间窗: Parts A and B: From the study baseline to 30 days after last dose of ARV-393; Parts C and D: From the study baseline to 40 days after last dose of ARV-393
Shifts in vital signs, ECGs, and laboratory parameters from study baseline
Percentage of Participants With Grade 3 or Grade 4 Clinical Lab Abnormalities Using the Common Terminology Criteria for Adverse Events (CTCAE) With Scale From Grade 1 Grade 5. Higher Score Means Worse Outcome
时间窗: Parts A and B: From the study baseline to 30 days after last dose of ARV-393; Parts C and D: From the study baseline to 40 days after last dose of ARV-393
Incidence of Grade 3 and Grade 4 clinical laboratory abnormalities
次要结局
- Area Under the Curve to the End of the Dosing Period (Auctau) for ARV-393(4 months from first drug dosing)
- Area Under the Concentration Versus Time Curve, from 0 To Last Measurable Concentration (AUC0-Last) for ARV-393(Time Frame: 4 months from first drug dosing)
- Maximum Concentration (Cmax) for ARV-393(4 months from first drug dosing)
- Minimum Concentration (Cmin) for ARV-393(4 months from first drug dosing)
- Time to Maximum Concentration (Tmax) for ARV-393(4 months from first drug dosing)
- Oral Clearance (CL/F) for ARV-393(4 months from first drug dosing)
- Volume of Distribution (Vd/F) for ARV-393(4 months from first drug dosing)
- Overall Response Rate (ORR) Based on Investigator Assessments of Response According to Lugano Response Criteria for NHL and International Primary Central Nervous System Lymphoma (PCNSL) Criteria for Central Nervous System (CNS Lymphoma), if Applicable(Approximately 2 years)
- Complete Response Rate (CRR) Based on Investigator Assessments of Response According to the Lugano Response Criteria for NHL and the International PCNSL Criteria for CNS Lymphoma, if Applicable(Approximately 2 years)
- Duration of Response (DOR) Based on Investigator Assessments of Response According to the Lugano Response Criteria for NHL and the International PCNSL Criteria for CNS Lymphoma, if Applicable(Approximately 2 years)