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临床试验/NCT04052997
NCT04052997已完成2 期

A Phase 2, Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of Camidanlumab Tesirine (ADCT-301) in Patients With Relapsed or Refractory Hodgkin Lymphoma

ADC Therapeutics S.A.73 个研究点 分布在 8 个国家目标入组 117 人开始时间: 2019年9月13日最近更新:
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适应症
干预措施
相关药物

试验速览

阶段
2 期
状态
已完成
入组人数
117
试验地点
73
主要终点
Overall Response Rate (ORR)
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The purpose of this study is to evaluate the clinical efficacy and safety of Camidanlumab Tesirine (ADCT-301) in participants with relapsed or refractory Hodgkin Lymphoma (HL).

详细描述

This is a phase 2, multi-center, open-label, single-arm study of efficacy and safety of Camidanlumab Tesirine (ADCT-301) in participants with relapsed or refractory Hodgkin lymphoma. This study will enroll approximately 100 participants.

Camidanlumab Tesirine (ADCT-301) is an antibody drug conjugate (ADC), composed of the human monoclonal antibody, HuMax®-TAC, which is directed against human CD25. The antibody is conjugated through a protease cleavable linker to SG3199, a pyrrolobenzodiazepine (PBD) dimer cytotoxin.

For each participant the study will include a screening period (of up to 28 days), a treatment period (cycles of 3 weeks), and a follow-up period (approximately every 12-week visits) for up to 3 years after treatment discontinuation.

Participants may continue treatment for up to 1 year or until disease progression, unacceptable toxicity, or other discontinuation criteria, whichever occurs first.

Additionally, patients benefiting clinically at 1 year may continue treatment after a case by case review with the Sponsor.

研究设计

研究类型
Interventional
分配方式
Na
干预模型
Single Group
主要目的
Treatment
盲法
None

入排标准

年龄范围
16 Years 至 —（Child, Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •Written informed consent must be obtained prior to any procedures.
  • •Male or female participant aged 18 years or older. (16 years or older at US based sites)
  • •Pathologic diagnosis of classical Hodgkin lymphoma (cHL).
  • •Patients with relapsed or refractory cHL, who have received at least 3 prior lines of systemic therapy (or at least 2 prior lines in HSCT ineligible patients) including brentuximab vedotin and a checkpoint inhibitor approved for cHL (e.g., nivolumab or pembrolizumab). Note 1: Receipt of HSCT to be included in the number of prior therapies needed to meet eligibility.
  • •Measurable disease as defined by the 2014 Lugano Classification.
  • •Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block (or minimum 10 freshly cut unstained slides if block is not available).
  • •Note 1: Any biopsy since initial diagnosis is acceptable, but if several samples are available, the most recent sample is preferred.
  • •Note 2: If a sufficient amount of tissue is not available, a fresh biopsy may be taken, provided the procedure is not deemed high-risk and is clinically feasible, and provided it is approved locally.
  • •Eastern Cooperative Oncology Group (ECOG) performance status 0-
  • •Adequate organ function as defined by Screening laboratory values within the following parameters:
  • •Absolute neutrophil count (ANC) ≥ 1.0 × 103/μL (off growth factors at least 72 h).
  • •Platelet count ≥ 75 × 103/μL without transfusion in the past 2 weeks.
  • •ALT, AST, or GGT ≤ 2.5 × the upper limit of normal (ULN) if there is no liver involvement; ALT or AST ≤ 5 × ULN if there is liver involvement.
  • •Total bilirubin ≤ 1.5 × ULN (participants with known Gilbert's syndrome may have a total bilirubin up to ≤ 3 × ULN with direct bilirubin ≤ 1.5 × ULN).
  • •Blood creatinine ≤ 3.0 × ULN or calculated creatinine clearance ≥ 30 mL/min by the Cockcroft-Gault equation.
  • •Note: A laboratory assessment may be repeated a maximum of two times during the Screening Period to confirm eligibility.
  • •Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 7 days prior to start of study drug for women of childbearing potential.
  • •Women of childbearing potential (WOCBP) must agree to use a highly effective method of contraception from the time of giving informed consent until at least 9.5 months after the last dose of Camidanlumab Tesirine. Men with female partners who are of childbearing potential must agree to use a highly effective method of contraception from the time of giving informed consent until at least 6.5 months after the participants receives his last dose of Camidanlumab Tesirine.

排除标准

  • •Previous treatment with Camidanlumab Tesirine.
  • •Participation in another investigational interventional study. Being in follow-up of another investigational study is allowed.
  • •Known history of hypersensitivity to or positive serum human anti-drug antibody (ADA) to a CD25 antibody.
  • •Allogenic or autologous transplant within 60 days prior to start of study drug.
  • •Active graft-versus-host disease (GVHD), except for non-neurologic symptoms as a manifestation of mild (≤ Grade 1) chronic GVHD.
  • •Post-transplantation lymphoproliferative disorders.
  • •Active second primary malignancy other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy that the Sponsor's medical monitor and Investigator agree and document should not be exclusionary.
  • •History of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, Sjögren's syndrome, autoimmune vasculitis [e.g., Wegener's granulomatosis]) (subjects with vitiligo, type 1 diabetes mellitus, residual hypothyroidism, hypophysitis due to autoimmune condition only requiring hormone replacement may be enrolled).
  • •History of neuropathy considered of autoimmune origin (e.g., polyradiculopathy including Guillain-Barré syndrome and myasthenia gravis) or other central nervous system autoimmune disease (e.g., poliomyelitis, multiple sclerosis).
  • •History of recent infection (within 4 weeks of Cycle 1, Day 1 [C1D1]) considered to be caused by one of the following pathogens: HSV1, HSV2, VZV, EBV, CMV, measles, Influenza A, Zika virus, Chikungunya virus, mycoplasma pneumonia, Campylobacter jejuni, or enterovirus D68, or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
  • •Note: An influenza test and a pathogendirected SARS CoV-2 test (such as polymerase chain reaction) are mandatory and must be negative before initiating study treatment (tests to be performed 3 days or less prior to dosing on C1D1; an additional 2 days are allowed in the event of logistical issues for receiving the results on time).
  • •Participants known to be or having been infected with human immunodeficiency (HIV) virus, hepatitis B virus (HBV), or hepatitis C virus (HCV), and require anti-viral therapy or prophylaxis. Note: Serology testing is mandatory for patients with unknown status.
  • •History of Stevens-Johnson syndrome or toxic epidermal necrolysis.
  • •Failure to recover ≤ Grade 1 (Common Terminology Criteria for Adverse Events version 4.0 [CTCAE v4.0]) from acute non-hematologic toxicity (except ≤ Grade 2 neuropathy or alopecia), due to previous therapy, prior to screening.
  • •Hodgkin lymphoma (HL) with central nervous system involvement, including leptomeningeal disease.
  • •Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath).
  • •Breastfeeding or pregnant.
  • •Significant medical comorbidities, including uncontrolled hypertension (blood pressure [BP] ≥ 160/100 mmHg repeatedly), unstable angina, congestive heart failure (greater than New York Heart Association class II), electrocardiographic evidence of acute ischemia, coronary angioplasty or myocardial infarction within 3 months prior to screening, severe uncontrolled atrial or ventricular cardiac arrhythmia, poorly controlled diabetes, or severe chronic pulmonary disease.
  • •Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy, within 14 days prior to start of study drug, except shorter if approved by the Sponsor.
  • •Use of any other experimental medication within 30 days prior to start of study drug.
  • •Any live vaccine within 4 weeks prior to start of study drug and planned live vaccine administration after starting study drug.
  • •Congenital long QT (measure between Q wave and T wave in the electrocardiogram) syndrome, or a corrected QTc interval of ≥ 480 ms, at screening (unless secondary to pacemaker or bundle branch block).
  • •Any other significant medical illness, abnormality, or condition that would, in the Investigator's judgment, make the participants inappropriate for study participation or put the participant at risk.

研究组 & 干预措施

Camidanlumab Tesirine

Experimental

Camidanlumab Tesirine is administered as a 30- minute intravenous (IV) infusion on Day 1 of each cycle (every 3 weeks). Camidanlumab Tesirine will be administered at a dose of 45 μg/kg every 3 weeks for 2 cycles, then 30 μg/kg for subsequent cycles.

干预措施: Camidanlumab Tesirine (Drug)

结局指标

主要结局

Overall Response Rate (ORR)

时间窗: Up to 3 years

ORR according to the 2014 Lugano classification as determined by central review in all-treated participants.ORR will be defined as the proportion of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). Data from the All-treated Population.

次要结局

  • Cmax of Camidanlumab Tesirine Unconjugated Warhead SG3199(Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h))
  • Area Under the Plasma Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) For Camidanlumab Tesirine Total Antibody(Cycle 2 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h))
  • AUCtau For Camidanlumab Tesirine PBD-Conjugated Antibody(Cycle 2 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h))
  • Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) For Camidanlumab Tesirine Total Antibody(Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h))
  • AUClast For Camidanlumab Tesirine PBD-Conjugated Antibody(Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h))
  • Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUCinf) For Camidanlumab Tesirine Total Antibody(Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h))
  • Duration of Response (DOR)(Up to 3 years)
  • Relapse-Free Survival (RFS)(Up to 3 years)
  • Progression-Free Survival (PFS)(Up to 3 years)
  • Number of Participants Who Experienced At Least One Serious Adverse Event (SAE)(Up to 3 years)
  • Maximum Observed Plasma Concentration (Cmax) of Camidanlumab Tesirine Total Antibody(Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h))
  • AUCtau For Camidanlumab Tesirine Unconjugated Warhead SG3199(Cycle 2 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h))
  • AUClast For Camidanlumab Tesirine Unconjugated Warhead SG3199(Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h))
  • AUCinf For Camidanlumab Tesirine PBD-Conjugated Antibody(Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h))
  • CR Rate(Up to 3 years)
  • Number of Participants Who Received Hematopoietic Stem Cell Transplant (HSCT)(Up to 3 years)
  • Cmax of Camidanlumab Tesirine PBD-Conjugated Antibody(Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h))
  • CLss For Camidanlumab Tesirine Unconjugated Warhead SG3199(Cycle 2 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h))
  • Number of Participants With Confirmed Positive Anti-Drug Antibody (ADA) Responses Post Dose(Up to 3 years)
  • Change From Baseline in HRQoL as Measured by Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym)(Baseline, Day 1 of Cycles 2 to 15 (one cycle = 21 days) and EOT (up to 3 years))
  • Overall Survival (OS)(Up to 3 years)
  • CL For Camidanlumab Tesirine Unconjugated Warhead SG3199(Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h))
  • Apparent Terminal Elimination Half-Life (T1/2) For Camidanlumab Tesirine Total Antibody(Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h))
  • T1/2 For Camidanlumab Tesirine PBD-Conjugated Antibody(Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h))
  • Volume of Distribution at Steady State (Vss) For Camidanlumab Tesirine Total Antibody(Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h))
  • Vss For Camidanlumab Tesirine PBD-Conjugated Antibody(Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h))
  • Vss For Camidanlumab Tesirine Unconjugated Warhead SG3199(Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h))
  • Number of Participants Who Experienced At Least One Treatment-Emergent Adverse Event (TEAE)(Up to 3 years)
  • Number of Participants With ECOG Performance Status Score of 0-3 at the End of Trial (EOT)(EOT (up to 3 years))
  • Clearance (CL) For Camidanlumab Tesirine Total Antibody(Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h))
  • Clearance at Steady State (CLss) For Camidanlumab Tesirine Total Antibody(Cycle 2 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h))
  • Change From Baseline in Health-Related Quality of Life (HRQoL) as Measured by EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS)(Baseline, Day 1 of Cycles 2 to 15 (one cycle = 21 days) and EOT (up to 3 years))
  • AUCinf For Camidanlumab Tesirine Unconjugated Warhead SG3199(Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h))
  • CL For Camidanlumab Tesirine PBD-Conjugated Antibody(Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h))
  • Accumulation Index (AI) For Camidanlumab Tesirine Total Antibody(Cycle 1 and 2: day 0 to 21)
  • AI For Camidanlumab Tesirine Unconjugated Warhead SG3199(Cycle 1 and 2: day 0 to 21)
  • CLss For Camidanlumab Tesirine PBD-Conjugated Antibody(Cycle 2 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h))
  • T1/2 For Camidanlumab Tesirine Unconjugated Warhead SG3199(Cycle 1 (one cycle = 21 days): day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h). Cycle 2: day 1 (predose, EOI, 4h postdose), day 8 (168h), day 15 (336h))
  • AI For Camidanlumab Tesirine PBD-Conjugated Antibody(Cycle 1 and 2: day 0 to 21)

研究者

申办方类型
Industry
责任方
Sponsor

研究点 (73)

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