Diffuse Large B-Cell Lymphoma RefractoryPhase 2LOTIS-2NCT03589469
Study to Evaluate the Efficacy and Safety of Loncastuximab Tesirine in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
A Phase 2 study testing Loncastuximab tesirine in people with Diffuse Large B-Cell Lymphoma Refractory and Diffuse Large B-cell Lymphoma Recurrent, run by ADC Therapeutics S.A. at 37 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B-Cell Lymphoma Refractory, Diffuse Large B-cell Lymphoma Recurrent
- What is being tested?
- Loncastuximab tesirine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 145 participants
- Where
- 37 sitesin 4 countries
- Study dates
- 1 Aug 2018to 9 Aug 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- Previous treatment with loncastuximab tesirine
- Known history of hypersensitivity to or positive serum human ADA to a CD19 antibody
- Pathologic diagnosis of Burkitt lymphoma
- 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
- 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)
Show all 21Show fewer
- 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
- Use of any other experimental medication within 14 days prior to start of study drug (C1D1)
- Planned live vaccine administration after starting study drug (C1D1)
- Failure to recover to Grade ≤1 (Common Terminology Criteria for Adverse Events version 4.0 [CTCAE v4.0]) from acute non-hematologic toxicity (Grade ≤2 neuropathy or alopecia) due to previous therapy prior to screening
- Congenital long QT syndrome or a corrected QTcF 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 patient inappropriate for study participation or put the patient at risk
Trial locations and contacts
37 sites in 4 countries.
37 sites in 4 countries
United States24 sites
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322
Northside Hospital
Atlanta, Georgia, 30342
Hollings Cancer Center
Charleston, South Carolina, 29425
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Baylor University Medical Center
Dallas, Texas, 75246
Medical Oncology & Hematology Associates
Des Moines, Iowa, 50309
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
Duarte, California, 91010
North Shore Hematology Oncology Associates DBA NY Cancer and Blood Specialists
East Setauket, New York, 11733
Virginia Cancer Specialists, PC
Fairfax, Virginia, 22031
Compassionate Care Research Group, Inc., at Compassionate Care Medical Group, Inc.
Fountain Valley, California, 92708
GHD Cancer Institute
Greenville, South Carolina, 29605
UC San Diego Moores Cancer Center
La Jolla, California, 92093
Northwest Georgia Oncology Centers, PC-Drug Shipment, Lab and Study Supplies Only
Marietta, Georgia, 30060
University of Miami Hospital and Clinics
Miami, Florida, 33136
Miami Cancer Institute
Miami, Florida, 33176
Froedtert Hospital & the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Ochsner Clinic Foundation
New Orleans, Louisiana, 70121
Vista Oncology Inc. PS
Olympia, Washington, 98506
University of Nebraska Medical Center/ Nebraska Medicine
Omaha, Nebraska, 68198
Sidney Kimmel Cancer Center at Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
University of California, San Francisco Medical Center
San Francisco, California, 94143
Washington University School of Medicine
St Louis, Missouri, 63110
Baylor Scott & White Medical Center - Temple
Temple, Texas, 76508
The Oncology Institute of Hope and Innovation
Whittier, California, 90602
United Kingdom7 sites
NHS Greater Glasgow and Clyde
Glasgow, Scotland, G120YN
University Hospitals of Leicester NHS Trust.
Leicester, England, LE1 5WW
University College London Hospital
London, England, NW1 2PG
The Christie NHS Foundation Trust
Manchester, England, M20 4BX
Nottingham University Hospitals NHS Trust
Nottingham, NG5 1 PB
Oxford Cancer Centre, Churchill Hospital
Oxford, England, OX3 7 LE
Abertawe Bro Morgannwg University Health Board - Singleton Hospital
Swansea, Wales, SA2 8QA
Italy5 sites
A.O. SS Antonio e Biagio e Cesare Arrigo
Alessandria, AL, 15121
Istituto di Ematologia Seragnoli
Bologna, BO, 40138
Dipartimento di Oncomatlolgia - Unita Linfomi
Milan, 20132
Divisione di Oncoematologia
Milan, 20141
U.O. Oncologia ed Ematologia
Rozzano, Milano, 20089
About this study
Official title: A Phase 2 Open-Label Single-Arm Study to Evaluate the Efficacy and Safety of Loncastuximab Tesirine in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) (LOTIS-2)
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.
Read the detailed description
This is a Phase 2, multi-center, open-label, single-arm study of the efficacy and safety of loncastuximab tesirine used as monotherapy in patients with relapsed or refractory DLBCL. The study will enroll approximately 140 patients
Loncastuximab Tesirine is an antibody drug conjugate (ADC) composed of a humanized antibody directed against human cluster of differentiation 19 (CD19), stochastically conjugated through a cathepsin-cleavable linker to SG3199, a pyrrolobenzodiazepine (PBD) dimer cytotoxin. Loncastuximab tesirine has been designed to target and kill CD19-expressing malignant B-cells.
A 2-stage design will be used in this clinical study, with an interim analysis for futility on the first 52 patients. If ≥10 patients respond (CR+PR), the study will proceed to complete full enrollment. Enrollment will continue during the interim analysis; however, further enrollment will be halted if futility is confirmed.
For each patient, 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).
Patients may continue treatment until disease progression, unacceptable toxicity, or other discontinuation criteria, whichever occurs first.
- Being tested
- Loncastuximab tesirine
- Keywords
- Loncastuximab tesirine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Loncastuximab tesirineDrug
Also called Zynlonta, ADCT-402
intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Loncastuximab tesirine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Up to 21.5 months
Secondary outcomes (20)
Duration of Response (DOR)
DOR defined as the time from the first documentation of tumor response to disease progression or death.
Measured: Up to 39 months
Complete Response (CR) Rate
CR rate defined as the percentage of treated participants with a best overall response (BOR) of CR.
Measured: Up to 39 months
Relapse-free Survival (RFS)
RFS was defined as the time from the documentation of CR to disease progression or death.
Measured: Up to 39 months
Progression-free Survival (PFS)
PFS was defined as the time between start of treatment and the first documentation of recurrence, progression, or death.
Measured: Up to 40 months
Overall Survival (OS)
OS was defined as the time between the start of treatment and death from any cause.
Measured: Up to 43 months
Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product that did not necessarily have to have a causal relationship with treatment. A TEAE was an adverse event with an onset that began or worsened on or after the first dose date and until 30 days after the last dose date, or start of a new anticancer therapy/procedure, whichever came earlier. TEAE assessments also included those per the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade ≥3 AEs and serious TEAEs.
AEs were graded using CTCAE version 4 and according to the following: Grade 1 = mild AE, Grade 2 = Moderate AE, Grade 3 = a severe AE, Grade 4 = life-threatening AE, and Grade 5 = death due to AE. For events not listed in the CTCAE criteria, the same grading was used.
Measured: Up to 599 days
Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Tests
Clinical laboratory tests included hematology and chemistry. Clinically significant changes were determined by the Investigator.
Measured: Baseline up to 599 days
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Vital sign measurements included arterial blood pressure, heart rate, respiratory rate, and body temperature. Clinical significance was determined by the investigator.
Measured: Baseline up to 599 days
Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline and End of Treatment
ECOG (Eastern Cooperative Oncology Group) Performance Status is scored on a 6-point scale where higher scores indicate a worse outcome. ECOG scores include the following:
- 0 = fully active, able to carry on all pre-disease performance without restriction
- 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
- 2 = ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours
- 3 = capable of only limited self-care; confined to bed or chair more than 50% of waking hours
- 4 = completely disabled; cannot carry on any self-care; totally confined to bed or chair
- 5 = dead
Measured: Baseline and end of treatment (up to 599 days)
Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiograms (ECGs)
Clinically significant changes from baseline for 12-lead ECGs were measured as abnormal QT interval corrected by Fridericia formula (QTcF) and QT interval corrected by Bazett formula (QTcB) values.
Measured: Baseline up to 599 days
Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
Measured: Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose and end of infusion
Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
Measured: Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose
Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-∞) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
Measured: Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose
Apparent Terminal Half-life (Thalf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
Measured: Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose
Apparent Clearance (CL) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
Measured: Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose
Apparent Volume of Distribution at Steady State (Vss) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
Measured: Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose
Accumulation Index (AI) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
AI is the ratio of AUC0-last for each cycle divided by AUC0-last of the previous cycle.
Measured: Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose
Number of Participants With an Anti-drug Antibody (ADA) Response to Loncastuximab Tesirine
Measured: Up to 599 days
Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS)
EQ-5D-5L is designed as an international, standardized, instrument for describing and evaluating quality of life (QoL). In the EQ-5D-5L VAS participants are asked to indicate their health state today on a VAS with the endpoints labeled 'the best health you can imagine' (score 100) and 'the worst health you can imagine' (score 0).
A higher score on the VAS indicates better health related QoL. A positive change from baseline indicates an improvement in health related QoL.
Measured: Baseline, Day 1 of Cycles 2 to 26 (cycle duration of 3 weeks), and end of treatment (up to 599 days)
Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS)
Composed of the Functional Assessment of Cancer Therapy - General (FACT-G) plus the 15-item LymS. The FACT-G questionnaire contains 27 items covering 4 core health related quality of life (QoL) subscales: Physical Wellbeing (7 items), Social/Family Wellbeing (7), Emotional Wellbeing (6), and Functional Wellbeing (7). The LymS addresses issues including pain, itching, night sweats, trouble sleeping, fatigue and trouble concentrating. Score range for the LymS was 0 - 60, where a higher score indicates less symptoms. The LymS score is reported. A positive change from baseline indicates an improvement in health related QoL.
Measured: Baseline, Day 1 of Cycles 2 to 25 (cycle duration of 3 weeks), and end of treatment (up to 599 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2018
- Study start1 Aug 2018
- Primary completion24 May 2020
- Study completion9 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Diffuse Large B-Cell Lymphoma RefractoryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 145 participants (actual)
Sponsor and investigators
- Lead sponsor
- ADC Therapeutics S.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03589469
- Sponsor's protocol ID
- ADCT-402-201
- Other IDs
- 2017-004288-11, 2017
- Acronym
- LOTIS-2
- Status last verified
- Aug 2023
- First submitted
- 4 May 2018
- Last updated
- 29 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 40669032Alderuccio 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.
PubMed 37855688Caimi 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.
PubMed 37646659Hamadani 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.
PubMed 35513980Hess 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.
PubMed 34893942Spira 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.
PubMed 34690090Caimi 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.
PubMed 33989558
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Open-Label Single-Arm Study to Evaluate the Efficacy and Safety of Loncastuximab Tesirine in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) (LOTIS-2)
- ClinicalTrials.gov ID
- NCT03589469
- Acronym / sponsor ID
- LOTIS-2 / ADCT-402-201
- Keywords
- Loncastuximab tesirine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 145 participants (actual)
- Lead sponsor
- ADC Therapeutics S.A.Industry (pharma, biotech, devices)
- Study start
- 1 Aug 2018 (actual)
- Primary completion
- 24 May 2020 (actual)
- Study completion
- 9 Aug 2022 (actual)
- First posted
- 18 Jul 2018 (actual)
- Results
- Posted 29 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a Phase 2, multi-center, open-label, single-arm study of the efficacy and safety of loncastuximab tesirine used as monotherapy in patients with relapsed or refractory DLBCL. The study will enroll approximately 140 patients
Loncastuximab Tesirine is an antibody drug conjugate (ADC) composed of a humanized antibody directed against human cluster of differentiation 19 (CD19), stochastically conjugated through a cathepsin-cleavable linker to SG3199, a pyrrolobenzodiazepine (PBD) dimer cytotoxin. Loncastuximab tesirine has been designed to target and kill CD19-expressing malignant B-cells.
A 2-stage design will be used in this clinical study, with an interim analysis for futility on the first 52 patients. If ≥10 patients respond (CR+PR), the study will proceed to complete full enrollment. Enrollment will continue during the interim analysis; however, further enrollment will be halted if futility is confirmed.
For each patient, 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).
Patients may continue treatment until disease progression, unacceptable toxicity, or other discontinuation criteria, whichever occurs first.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Loncastuximab tesirine | Experimental | Drug: Loncastuximab tesirineParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (21 listed)
- Previous treatment with loncastuximab tesirine
- Known history of hypersensitivity to or positive serum human ADA to a CD19 antibody
- Pathologic diagnosis of Burkitt lymphoma
- 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
- Autologous stem cell transplant (ASCT) within 30 days prior to start of study drug (C1D1)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Loncastuximab tesirineAlso: Zynlonta, ADCT-402intravenous infusion | Drug | Loncastuximab tesirine |
Primary outcome
Overall Response Rate (ORR)
Time frame: Up to 21.5 months
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).
20 secondary outcomes
Duration of Response (DOR)
Time frame: Up to 39 months
Complete Response (CR) Rate
Time frame: Up to 39 months
Relapse-free Survival (RFS)
Time frame: Up to 39 months
Progression-free Survival (PFS)
Time frame: Up to 40 months
Overall Survival (OS)
Time frame: Up to 43 months
Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs)
Time frame: Up to 599 days
Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Tests
Time frame: Baseline up to 599 days
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Time frame: Baseline up to 599 days
Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline and End of Treatment
Time frame: Baseline and end of treatment (up to 599 days)
Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiograms (ECGs)
Time frame: Baseline up to 599 days
Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
Time frame: Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose and end of infusion
Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
Time frame: Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose
Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-∞) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
Time frame: Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose
Apparent Terminal Half-life (Thalf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
Time frame: Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose
Apparent Clearance (CL) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
Time frame: Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose
Apparent Volume of Distribution at Steady State (Vss) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
Time frame: Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose
Accumulation Index (AI) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199
Time frame: Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose
Number of Participants With an Anti-drug Antibody (ADA) Response to Loncastuximab Tesirine
Time frame: Up to 599 days
Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS)
Time frame: Baseline, Day 1 of Cycles 2 to 26 (cycle duration of 3 weeks), and end of treatment (up to 599 days)
Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS)
Time frame: Baseline, Day 1 of Cycles 2 to 25 (cycle duration of 3 weeks), and end of treatment (up to 599 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40669032Kuker 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.
- Derived from this study: PubMed 37855688Alderuccio 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.
- Derived from this study: PubMed 37646659Caimi 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.
- Derived from this study: PubMed 35513980Hamadani 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.
- Derived from this study: PubMed 34893942Hess 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.
- Derived from this study: PubMed 34690090Spira 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.
- Derived from this study: PubMed 33989558Caimi 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
37 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Loncastuximab tesirine in people with Diffuse Large B-Cell Lymphoma Refractory and Diffuse Large B-cell Lymphoma Recurrent, run by ADC Therapeutics S.A. at 37 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 37 sites in United States, United Kingdom, Italy, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (ORR) (time frame: Up to 21.5 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03589469, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2023.