Study to Evaluate the Efficacy and Safety of Loncastuximab Tesirine in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

NCT03589469 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: ADCT-402-2012017-004288-11
• Study Type: interventional
• Target: 145
• Locations: 4 countries
• Sites: 37

Brief Summary

The purpose of this Phase 2 study is to evaluate the clinical efficacy and safety of Loncastuximab Tesirine (ADCT-402) in patients with relapsed or refractory Diffuse Large B-Cell Lymphoma.

Conditions

Diffuse Large B-Cell Lymphoma Refractory; Diffuse Large B-cell Lymphoma Recurrent

Keywords

Loncastuximab tesirine

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  ORR, as determined by central review according to the 2014 Lugano classification, defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR).

  Up to 21.5 months

Secondary Outcomes (20)

• Duration of Response (DOR)

  Up to 39 months

• Complete Response (CR) Rate

  Up to 39 months

• Relapse-free Survival (RFS)

  Up to 39 months

• Progression-free Survival (PFS)

  Up to 40 months

• Overall Survival (OS)

  Up to 43 months

Study Arms (1)

Loncastuximab tesirine

EXPERIMENTAL

Participants will receive loncastuximab tesirine as an IV infusion over 30 minutes on Day 1 of each cycle (every 3 weeks) at a dose of 150 μg/kg Q3W for 2 cycles, then 75 μg/kg Q3W for subsequent cycles for up to one year or until disease progression, unacceptable toxicity, or other discontinuation criteria, whichever occurs first.

Drug: Loncastuximab tesirine

Interventions

Loncastuximab tesirine DRUG

intravenous infusion

Also known as: Zynlonta, ADCT-402

Loncastuximab tesirine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patient aged 18 years or older.
• Pathologic diagnosis of DLBCL, as defined by the 2016 WHO classification, to include: DLBCL not otherwise specified; primary mediastinal large B-cell lymphoma; and high-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements
• Relapsed or refractory disease following two or more multi-agent systemic treatment regimens
• Patients who have received previous CD19-directed therapy must have a biopsy that shows CD19 protein expression after completion of the CD19-directed therapy.
• 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
• ECOG performance status 0-2
• Adequate organ function
• Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 7 days prior to start of study drug (C1D1) for women of childbearing potential
• Women of childbearing potential must agree to use a highly effective method of contraception from the time of giving informed consent until at least 16 weeks after the last dose of loncastuximab tesirine. Men with female partners who are of childbearing potential must agree that they will use a highly effective method of contraception from the time of giving informed consent until at least 16 weeks after the patient receives his last dose of loncastuximab tesirine.

You may not qualify if:

• Previous treatment with loncastuximab tesirine
• Known history of hypersensitivity to or positive serum human ADA to a CD19 antibody
• Pathologic diagnosis of Burkitt lymphoma
• Autologous stem cell transplant (ASCT) within 30 days prior to start of study drug (C1D1)
• Allogeneic stem cell transplant (AlloSCT) within 60 days prior to start of study drug (C1D1)
• Active graft-versus-host disease
• Post-transplant lymphoproliferative disorders
• Active autoimmune disease, including motor neuropathy considered of autoimmune origin and other central nervous system (CNS) autoimmune disease
• Known seropositive and requiring anti-viral therapy for human immunodeficiency (HIV) virus, hepatitis B virus (HBV), or hepatitis C virus (HCV).
• History of Stevens-Johnson syndrome or toxic epidermal necrolysis
• Lymphoma with active CNS involvement at the time of screening, 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
• Major surgery, radiotherapy, chemotherapy or other anti-neoplastic therapy within 14 days prior to start of study drug (C1D1), except shorter if approved by the Sponsor

Sponsors & Collaborators

• ADC Therapeutics S.A.: lead

Study Sites (37)

City of Hope (City of Hope National Medical Center, City of Hope Medical Center)

Duarte, California, 91010, United States

Location

Compassionate Care Research Group, Inc., at Compassionate Care Medical Group, Inc.

Fountain Valley, California, 92708, United States

Location

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

University of California, San Francisco Medical Center

San Francisco, California, 94143, United States

Location

The Oncology Institute of Hope and Innovation

Whittier, California, 90602, United States

Location

University of Miami Hospital and Clinics

Miami, Florida, 33136, United States

Location

Miami Cancer Institute

Miami, Florida, 33176, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Northwest Georgia Oncology Centers, PC-Drug Shipment, Lab and Study Supplies Only

Marietta, Georgia, 30060, United States

Location

Medical Oncology & Hematology Associates

Des Moines, Iowa, 50309, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center/ Nebraska Medicine

Omaha, Nebraska, 68198, United States

Location

North Shore Hematology Oncology Associates DBA NY Cancer and Blood Specialists

East Setauket, New York, 11733, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Sidney Kimmel Cancer Center at Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

GHD Cancer Institute

Greenville, South Carolina, 29605, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

Baylor Scott & White Medical Center - Temple

Temple, Texas, 76508, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Vista Oncology Inc. PS

Olympia, Washington, 98506, United States

Location

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

A.O. SS Antonio e Biagio e Cesare Arrigo

Alessandria, AL, 15121, Italy

Location

Istituto di Ematologia Seragnoli

Bologna, BO, 40138, Italy

Location

U.O. Oncologia ed Ematologia

Rozzano, Milano, 20089, Italy

Location

Dipartimento di Oncomatlolgia - Unita Linfomi

Milan, 20132, Italy

Location

Divisione di Oncoematologia

Milan, 20141, Italy

Location

Anastasios Stathis

Bellinzona, Canton Ticino, 6500, Switzerland

Location

University Hospitals of Leicester NHS Trust.

Leicester, England, LE1 5WW, United Kingdom

Location

University College London Hospital

London, England, NW1 2PG, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, England, M20 4BX, United Kingdom

Location

Oxford Cancer Centre, Churchill Hospital

Oxford, England, OX3 7 LE, United Kingdom

Location

NHS Greater Glasgow and Clyde

Glasgow, Scotland, G120YN, United Kingdom

Location

Abertawe Bro Morgannwg University Health Board - Singleton Hospital

Swansea, Wales, SA2 8QA, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, NG5 1 PB, United Kingdom

Location

Related Publications (7)

• Kuker RA, Alderuccio JP, Han S, Polar MK, Crane TE, Moskowitz CH, Yang F. Deep Learning-Based Body Composition Analysis for Outcome Prediction in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Insights From the LOTIS-2 Trial. JCO Clin Cancer Inform. 2025 Jul;9:e2500051. doi: 10.1200/CCI-25-00051. Epub 2025 Jul 16.

  PMID: 40669032 DERIVED

• Alderuccio JP, Reis IM, Hamadani M, Nachiappan M, Leslom S, Kahl BS, Ai WZ, Radford J, Solh M, Ardeshna KM, Hess BT, Lunning MA, Zinzani PL, Stathis A, Carlo-Stella C, Lossos IS, Caimi PF, Han S, Yang F, Kuker RA, Moskowitz CH. PET/CT Biomarkers Enable Risk Stratification of Patients with Relapsed/Refractory Diffuse Large B-cell Lymphoma Enrolled in the LOTIS-2 Clinical Trial. Clin Cancer Res. 2024 Jan 5;30(1):139-149. doi: 10.1158/1078-0432.CCR-23-1561.

  PMID: 37855688 DERIVED

• Caimi PF, Ai WZ, Alderuccio JP, Ardeshna KM, Hamadani M, Hess B, Kahl BS, Radford J, Solh M, Stathis A, Zinzani PL, Wang Y, Qin Y, Wang L, Xu ZC, Carlo-Stella C. Loncastuximab tesirine in relapsed/refractory diffuse large B-cell lymphoma: long-term efficacy and safety from the phase II LOTIS-2 study. Haematologica. 2024 Apr 1;109(4):1184-1193. doi: 10.3324/haematol.2023.283459.

  PMID: 37646659 DERIVED

• Hamadani M, Chen L, Song Y, Xu MK, Liao L, Caimi PF, Carlo-Stella C. Matching-adjusted Indirect Comparison of the Efficacy of Loncastuximab Tesirine Versus Treatment in the Chemoimmunotherapy Era for Relapsed/Refractory Diffuse Large B-cell Lymphoma. Clin Lymphoma Myeloma Leuk. 2022 Aug;22(8):e738-e744. doi: 10.1016/j.clml.2022.04.006. Epub 2022 Apr 8.

  PMID: 35513980 DERIVED

• Hess B, Townsend W, Ai W, Stathis A, Solh M, Alderuccio JP, Ungar D, Liao S, Liao L, Khouri L, Zhang X, Boni J. Efficacy and Safety Exposure-Response Analysis of Loncastuximab Tesirine in Patients with B cell non-Hodgkin Lymphoma. AAPS J. 2021 Dec 10;24(1):11. doi: 10.1208/s12248-021-00660-3.

  PMID: 34893942 DERIVED

• Spira A, Zhou X, Chen L, Gnanasakthy A, Wang L, Ungar D, Curiel R, Liao L, Radford J, Kahl B. Health-Related Quality of Life, Symptoms, and Tolerability of Loncastuximab Tesirine in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Clin Lymphoma Myeloma Leuk. 2022 Mar;22(3):158-168. doi: 10.1016/j.clml.2021.09.001. Epub 2021 Sep 22.

  PMID: 34690090 DERIVED

• Caimi PF, Ai W, Alderuccio JP, Ardeshna KM, Hamadani M, Hess B, Kahl BS, Radford J, Solh M, Stathis A, Zinzani PL, Havenith K, Feingold J, He S, Qin Y, Ungar D, Zhang X, Carlo-Stella C. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):790-800. doi: 10.1016/S1470-2045(21)00139-X. Epub 2021 May 11.

  PMID: 33989558 DERIVED

MeSH Terms

Interventions

loncastuximab tesirine

Results Point of Contact

• Title: Clinical Trials Information
• Organization: ADC Therapeutics SA

clinical.trials@adctherapeutics.com

954-903-7994

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2018
• First Posted: July 18, 2018
• Study Start: August 1, 2018
• Primary Completion: May 24, 2020
• Study Completion: August 9, 2022
• Last Updated: August 29, 2023
• Results First Posted: July 29, 2021

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1); GB (7); IT (5); US (24)