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临床试验 NCT04970901 针对B细胞非霍奇金淋巴瘤,Relapsed B-Cell Non-Hodgkin Lymphoma,难治性B细胞非霍奇金淋巴瘤目前招募中。请查看临床试验雷达卡片视图和 AI 发现工具了解所有详情,或在此提出任何问题。
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A Study to Evaluate the Safety and Anti-cancer Activity of Loncastuximab Tesirine in Combination With Other Anti-cancer Agents in Participants With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (LOTIS-7) I期 200

招募中
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临床试验NCT04970901旨在研究治疗,主要针对B细胞非霍奇金淋巴瘤,Relapsed B-Cell Non-Hodgkin Lymphoma,难治性B细胞非霍奇金淋巴瘤。这是一项I期 干预性研究试验,目前试验状态为招募中。试验始于2022年6月17日,计划招募200名患者。该研究由ADC Therapeutics主导,预计于2027年10月29日完成。试验数据来源于ClinicalTrials.gov,最后更新时间为2026年3月13日
简要概括
The primary objective of this study is to characterize the safety and tolerability of loncastuximab tesirine in combination with polatuzumab vedotin, glofitamab, or mosunetuzumab, and to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) for the combinations.
详细描述
This is a Phase 1b, multi-center, open-label, multi-arm study to evaluate the safety and anti-cancer activity of loncastuximab tesirine in combination with polatuzumab vedotin, glofitamab, or mosunetuzumab in participants with relapsed or refractory B-cell Non-Hodgkin Lymphoma (R/R B-NHL). The study will enroll approximately 200 participants.

Loncastuximab tesirine (ADCT-402; Zynlonta) is an antibody drug conjugate ...

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官方标题

A Phase 1b Open-Label Study to Evaluate the Safety and Anti-cancer Activity of Loncastuximab Tesirine in Combination With Other Anti-cancer Agents in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (LOTIS-7)

疾病
B细胞非霍奇金淋巴瘤Relapsed B-Cell Non-Hodgkin Lymphoma难治性B细胞非霍奇金淋巴瘤
其他研究标识符
  • ADCT-402-105
  • 2021-001071-16 (EudraCT 编号)
NCT编号
实际开始日期
2022-06-17
最近更新发布
2026-03-13
预计完成日期
2027-10-29
计划入组人数
200
研究类型
干预性研究
试验分期 (阶段)
I期
试验状态
招募中
关键词
B-Cell Non-Hodgkin Lymphoma
Relapsed B-Cell Non-Hodgkin Lymphoma
Refractory B-Cell Non-Hodgkin Lymphoma
Loncastuximab Tesirine
主要目的
治疗方法
分配方式
非随机
干预模型
序贯设计
盲法
无(开放性试验)
试验组/干预措施
参与者组/试验组干预措施/治疗方法
实验性Part 1 (Dose Escalation): Loncastuximab Tesirine + Polatuzumab Vedotin (Arm C)
Participants will receive escalating doses (90 µg/kg to 150 µg/kg) of loncastuximab tesirine on Day (D) 1 of each cycle (where each cycle is 21 days). Participants will also receive polatuzumab vedotin at a dose of 1.8 mg/kg on D1 of each cycle, infusion will be started one hour after end of loncastuximab tesirine infusion.
Loncastuximab Tesirine
Intravenous (IV) infusion
Polatuzumab Vedotin
IV infusion
实验性Part 1 (Dose Escalation): Loncastuximab Tesirine + Glofitamab (Arm E)
Participants will receive escalating doses (90 µg/kg to 150 µg/kg) of loncastuximab tesirine on D2 of Cycle (C) 1 and then D1 of all other cycles (where each cycle is 21 days). Participants will also receive glofitamab 2.5 mg on C1 D8, 10 mg on C1 D15 and 30 mg for cycles 2-12 D1. In addition participants will receive obinutuzumab pre-treatment 1000 mg on C1 D1.
Loncastuximab Tesirine
Intravenous (IV) infusion
Glofitamab
IV infusion
Obinutuzumab
IV infusion
实验性Part 1 (Dose Escalation): Loncastuximab Tesirine + Mosunetuzumab (Arm F)
Participants will receive escalating doses (90 µg/kg to 150 µg/kg) of loncastuximab tesirine on Day (D) 1 of each cycle (where each cycle is 21 days). Participants will also receive mosunetuzumab 5 mg on C1 D1, 45 mg for C1 D8, C1 D15 and cycles 2-8 D1.
Loncastuximab Tesirine
Intravenous (IV) infusion
Mosunetuzumab
Subcutaneous (SC) injection
实验性Part 2 (Dose Expansion): Loncastuximab Tesirine + Polatuzumab Vedotin (Arm C)
Participants with B-NHL will receive loncastuximab tesirine in combination with polatuzumab vedotin at the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) if favorable results of Part 1 are received.
Loncastuximab Tesirine
Intravenous (IV) infusion
Polatuzumab Vedotin
IV infusion
实验性Part 2 (Dose Expansion): Loncastuximab Tesirine + Glofitamab (Arm E)
Participants with B-NHL will receive loncastuximab tesirine in combination with glofitamab at the MTD and/or RDE if favorable results of Part 1 are received. In addition participants will receive obinutuzumab pre-treatment 1000 mg on C1 D1.
Loncastuximab Tesirine
Intravenous (IV) infusion
Glofitamab
IV infusion
Obinutuzumab
IV infusion
实验性Part 2 (Dose Expansion): Loncastuximab Tesirine + Mosunetuzumab (Arm F)
Participants with B-NHL will receive loncastuximab tesirine in combination with mosunetuzumab at the MTD and/or RDE if favorable results of Part 1 are received.
Loncastuximab Tesirine
Intravenous (IV) infusion
Mosunetuzumab
Subcutaneous (SC) injection
主要终点
结果指标度量标准描述时间框架
Number of Participants Who Experience a Dose-Limiting Toxicity (DLT)
Day 1 to Day 21 of Cycle 1, where a cycle is 21 days
Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)
Frequency and severity of TEAEs and treatment-emergent serious adverse events (TESAEs). TEAEs and TESAEs will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
Up to approximately 2 years for Arm C and 3 years for Arms E and F
Number of Participants Who Experience an Adverse Event (AE) Leading to Dose Delay
Up to approximately 1 year
Number of Participants Who Experience an Adverse Event (AE) Leading to Dose Interruption
Up to approximately 1 year
Number of Participants Who Experience an Adverse Event (AE) Leading to Dose Reduction
Up to approximately 1 year
Number of Participants Who Experience a Clinically Significant Change from Baseline in Safety Laboratory Measurements
Baseline up to approximately 1 year
Number of Participants Who Experience a Clinically Significant Change from Baseline in Vital Signs
Baseline up to approximately 1 year
Number of Participants Who Experience a Clinically Significant Change from Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status
ECOG performance status will be measured on a scale from grades 0-5, where a higher grade indicates a worse outcome.
Baseline up to approximately 1 year
Number of Participants Who Experience a Clinically Significant Change from Baseline in 12-Lead Electrocardiogram (ECG) Measurements
Baseline up to approximately 1 year
次要终点
结果指标度量标准描述时间框架
Complete Response Rate (CRR)
Up to approximately 2 years for Arm C and 3 years for Arms E and F
Overall Response Rate (ORR)
Up to approximately 2 years for Arm C and 3 years for Arms E and F
Duration of Response (DOR)
Up to approximately 2 years for Arm C and 3 years for Arms E and F
Progression-Free Survival (PFS)
Up to approximately 2 years for Arm C and 3 years for Arms E and F
Relapse-Free Survival (RFS)
Up to approximately 2 years for Arm C and 3 years for Arms E and F
Overall Survival (OS)
Up to approximately 2 years for Arm C and 3 years for Arms E and F
Average Concentration of Loncastuximab Tesirine
Day 1 to end of treatment (up to approximately 1 year)
Maximum Concentration (Cmax) of Loncastuximab Tesirine
Day 1 to end of treatment (up to approximately 1 year)
Time to Maximum Concentration (Tmax) of Loncastuximab Tesirine
Day 1 to end of treatment (up to approximately 1 year)
Area Under the Concentration-Time Curve from Time Zero to the Last Quantifiable Concentration (AUClast) of Loncastuximab Tesirine
Day 1 to end of treatment (up to approximately 1 year)
Area Under the Concentration-Time Curve from Time Zero to the End of the Dosing Interval (AUCtau) of Loncastuximab Tesirine
Day 1 to end of treatment (up to approximately 1 year)
Area Under the Concentration-Time Curve from Time Zero to Infinity (AUCinf) of Loncastuximab Tesirine
Day 1 to end of treatment (up to approximately 1 year)
Apparent Terminal Elimination Half-Life (Thalf) of Loncastuximab Tesirine
Day 1 to end of treatment (up to approximately 1 year)
Apparent Clearance (CL) of Loncastuximab Tesirine
Day 1 to end of treatment (up to approximately 1 year)
Apparent Steady-State Volume of Distribution (Vss) of Loncastuximab Tesirine
Day 1 to end of treatment (up to approximately 1 year)
Accumulation Index (AI) of Loncastuximab Tesirine
Day 1 to end of treatment (up to approximately 1 year)
Number of Participants With Anti-Drug Antibody (ADA) Titers to Loncastuximab Tesirine
Day 1 to end of treatment (up to approximately 1 year)
Arm E Only: Number of Participants With ADA Titers to Glofitamab
Day 1 to end of treatment (up to approximately 1 year)
Arm F Only: Number of Participants With ADA Titers to Mosunetuzumab
Day 1 to end of treatment (up to approximately 1 year)
参与助手
资格标准

适龄参与研究
成人, 老年人
最低年龄要求
18 Years
适龄性别
全部
  • Male or female participant aged 18 years or older

  • Pathologic diagnosis of relapsed (disease that has recurred following a response) or refractory (disease that failed to respond to prior therapy) B-NHL (2016 World Health Organization classification) who have failed, or been intolerant to any approved therapy and had received at least two systemic treatment regimens in Part 1; and at least one systemic treatment regimen in Part 2

    • LBCL:

Part 2 Arm E enrollment focused on LBCL only

  • DLBCL, not otherwise specified (NOS)

  • Germinal Center B-cell type

  • Activated B-cell type

  • Transformed FL (note: patients with transformed FL must have received at least one line of systemic therapy post-transformation to be eligible)

  • HGBCL, with MYC and BCL2 and/or BCL6 rearrangements

  • HGBCL, NOS

  • FL Grade 3b

    • Arm F and Part 1 Arm E:
  • All LBCL histologies listed above

  • FL (Grade 1-3a)

  • MZL

    • For Arm C only:
  • All histologies listed above

  • DLBCL (including transformed diseases)

  • MCL

  • BL

    • Life expectancy of at least 24 weeks according to Investigator's judgement
    • Need of systemic treatment for any of the listed indications as assessed by the investigator, including indolent B-NHLs (e.g. FL and MZL)
    • Measurable disease as defined by the 2014 Lugano Classification
    • Availability of formalin-fixed paraffin-embedded tumor tissue block
    • ECOG performance status 0 to 2
    • Adequate organ function
    • 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 10 months after the last dose of loncastuximab tesirine. Men with female partners who are of childbearing potential must agree to use a condom when sexually active or practice total abstinence from the time of giving informed consent the first dose until at least 7 months after the last dose of loncastuximab tesirine. Men must refrain from donating sperm during this same period. Arm E: WOCBP must agree to use contraceptive methods that result in a failure of less than 1% per year or remain abstinent (refrain from heterosexual intercourse) during the treatment period and for at least 18 months after pretreatment with obinutuzumab. Arm F: WOCBP must agree to use contraceptive methods that result in a failure of less than 1% per year or remain abstinent (refrain from heterosexual intercourse) during the treatment period and for at least 3 months after the final dose of mosunetuzumab and tocilizumab (if applicable)
    • Patients 80 years of age and older at the time of signing the informed consent must be deemed fit by Cumulative Illness Rating Scale - Geriatric (CIRS-G scale), defined as no score of 3-4 in any category AND < 5 categories with a score of 2 excluding hematologic criteria

  • Known history of hypersensitivity resulting in treatment discontinuation to or positive serum human ADA to a CD19 antibody

  • Previous therapy with loncastuximab tesirine

  • Previous treatment with polatuzumab vedotin, glofitamab or mosunetuzumab (applied to relevant arm and/or cohort of the specific drug administered)

    • Participants who received previous treatment of polatuzumab vedotin containing regimen will be excluded from Arm C
    • Participants who received previous treatment of glofitamab containing regimen will be excluded from Arm E
    • Participants who received previous treatment of mosunetuzumab containing regimen will be excluded from Arm F
  • Human immunodeficiency virus (HIV) seropositive

  • Serologic evidence of chronic hepatitis B virus (HBV) infection and unable or unwilling to receive standard prophylactic antiviral therapy or with detectable HBV viral load

  • Serologic evidence of hepatitis C virus (HCV) infection without completion of curative treatment or with detectable HCV viral load

  • History of confirmed progressive multifocal leukoencephalopathy

  • History of Stevens-Johnson syndrome, toxic epidermal necrolysis, or macrophage activation syndrome (MAS)/hemophagocytic lymphohistiocytosis (HLH)

  • 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

  • Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy, within 14 days prior to start of study drugs (C1 D1), unless approved by the Sponsor

  • Live vaccine within 4 weeks prior to C1D1

  • Failure to recover to Grade ≤1 (Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0) from acute non-hematologic toxicity (excluding alopecia) due to previous therapy prior to screening

  • 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

Extra Exclusion Criteria for Arms E (includes glofitamab) and F (includes mosunetuzumab) Note: as applicable, the arm-specific exclusion criteria may supersede the general ones, such as stem cell transplant.

  • Prior allogeneic stem cell transplant and solid organ transplant
  • Autologous stem cell transplant within 100 days prior to C1D1
  • History of central nervous system (CNS) lymphoma or leptomeningeal infiltration
  • Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
  • Known active infection, reactivation of a latent infection, whether bacterial, viral, fungal, mycobacterial, or other pathogens (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization or treatment with intravenous (IV) antibiotics within four weeks prior to C1D1
  • Active or history of autoimmune disease or immune deficiency, motor neuropathy considered of autoimmune origin and other CNS autoimmune diseases, including but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with, with certain exceptions
  • Prior treatment with anti-cancer/lymphoma targeted therapies (e.g., tyrosine kinase inhibitors, systemic immunotherapeutic/immunostimulating agents, including, but not limited to, cluster of differentiation 137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), anti-programmed cell death protein 1 (PD1), and anti-programmed death ligand 1 (PDL1) therapeutic antibodies, radio-immunoconjugates, ADCs, immune/cytokines and monoclonal antibodies) or treatment with systemic immunosuppressive medication (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to C1D1, or anticipation of need for systemic immunosuppressive medication during study treatment, with certain exceptions
  • Prior treatment with CAR-T-cell therapy within 100 days prior to C1D1; primary refractory patients (progressive or persistent disease within 30 days) to CAR-T-cell therapy are not eligible
  • Toxicities from prior anti-cancer therapy including immunotherapy that did not resolve to ≤ Grade 1 with the exception of alopecia, endocrinopathy managed with replacement therapy and stable vitiligo
  • Any history of immune-related Grade ≥3 AE with the exception of endocrinopathy managed with replacement therapy
  • Ongoing corticosteroid use greater than 25 mg/day of prednisone or equivalent within 4 weeks prior and during study treatment
  • Administration of a live attenuated vaccine within 4 weeks prior to the first dose of study treatment or anticipation that such a live attenuated vaccine will be required during the study or within 5 months after last dose of study treatment
  • Arm E only: Known history of hypersensitivity to obinutuzumab
ADC Therapeutics S.A. logoADC Therapeutics
研究中心联系人
联系人: Contact ADC Therapeutics, 954-903-7994, [email protected]
42 位于 6 个国家/地区的研究中心

California

University of California San Francisco - Fresno Center for Medical Education and Research, Clovis, California, 93611, United States
招募中
Scripps Health - Prebys Cancer Center, San Diego, California, 92103, United States
招募中

Florida

Sylvester Comprehensive Cancer Center, Miami, Florida, 33136, United States
招募中
Miami Cancer Institute, Miami, Florida, 33176, United States
招募中
Memorial Cancer Institute - Memorial Hospital West, Pembroke Pines, Florida, 33028, United States
招募中

Georgia

Winship Cancer Institute of Emory University, Atlanta, Georgia, 30322, United States
招募中
The Blood and Marrow Transplant Group of Georgia, Atlanta, Georgia, 30342, United States
招募中

Iowa

Mission Cancer + Blood - Mission Cancer Foundation, Des Moines, Iowa, 50309, United States
招募中

Massachusetts

Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02215, United States
招募中
Dana-Farber Cancer Institute, Boston, Massachusetts, 02215, United States
招募中

Minnesota

University of Minnesota, Minneapolis, Minnesota, 55455, United States
招募中

New York

Columbia University Irving Medical Center, New York, New York, 10027, United States
招募中

Ohio

Cleveland Clinic Main Campus, Cleveland, Ohio, 44195, United States
招募中

Oregon

Oregon Health and Science University, Portland, Oregon, 97239, United States
招募中

Pennsylvania

Penn Medicine - Perelman Center for Advanced Medicine, Philadelphia, Pennsylvania, 19104, United States
招募中
Allegheny Health Network - West Penn Hospital, Pittsburgh, Pennsylvania, 15224, United States
招募中

Rhode Island

Brown University Health - Rhode Island Hospital, Providence, Rhode Island, 02903, United States
招募中

South Carolina

Hollings Cancer Center, Charleston, South Carolina, 29425, United States
已完成

South Dakota

Avera Cancer Institute, Sioux Falls, South Dakota, 57105, United States
已撤回

Tennessee

Greco-Hainsworth Tennessee Oncology Centers for Research (GHCR), Nashville, Tennessee, 37203, United States
招募中

Texas

Baylor University Medical Center, Dallas, Texas, 75246, United States
招募中

Utah

Huntsman Cancer Institute, Salt Lake City, Utah, 84112, United States
招募中

Virginia

Emily Couric Clinical Cancer Center, Charlottesville, Virginia, 22903, United States
招募中
NEXT Virginia (Virginia Cancer Specialists), Fairfax, Virginia, 22031, United States
已完成

Wisconsin

Froedtert & Medical College of Wisconsin, Milwaukee, Wisconsin, 53226, United States
招募中
Universitair Ziekenhuis Gent, Ghent, 9000, Belgium
招募中
Centre Hospitalier Universitaire Universite Catholique de Louvain - Site Godinne, Yvoir, B-5530, Belgium
招募中

South Moravian

Fakultni Nemocnice Brno, Brno, South Moravian, 625 00, Czechia
已撤回
Fakultni nemocnice Ostrava, Ostrava, 708 52, Czechia
招募中
Fakultní Nemocnice Královské Vinohrady, Prague, 100 34, Czechia
招募中
Fakultni nemocnice v Motole, Prague, 150 06, Czechia
招募中
Azienda Socio Sanitaria Territoriale (ASST) Papa Giovanni XXIII, Bergamo, 24127, Italy
招募中
Centro di Ricerche Cliniche - IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, 40138, Italy
招募中
Azienda Socio Sanitaria Territoriale (ASST) degli Spedali Civili di Brescia, Brescia, 25123, Italy
招募中
Istituto Europeo di Oncologia, Milan, 20141, Italy
招募中
Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet), Barcelona, 08908, Spain
招募中
Hospital General Universitario Gregorio Marañón, Madrid, 28007, Spain
招募中
Hospital Universitario Ramón y Cajal, Madrid, 28034, Spain
招募中
Complejo Asistencial Universitario de Salamanca - Hospital Clínico, Salamanca, 37007, Spain
招募中
Hospital Universitari i Politècnic La Fe, Valencia, 46026, Spain
招募中
University College London Hospitals NHS Foundation Trust, London, NW1 2PG, United Kingdom
已完成
Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 7LE, United Kingdom
已完成