Relapsed Diffuse Large B-Cell LymphomaPhase 3LOTIS 5NCT04384484
Study to Evaluate Loncastuximab Tesirine With Rituximab Versus Immunochemotherapy in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
A Phase 3 study testing Loncastuximab Tesirine, Rituximab and Gemcitabine in people with Relapsed Diffuse Large B-Cell Lymphoma and Refractory Diffuse Large B-Cell Lymphoma, run by ADC Therapeutics S.A. at 144 sites in 21 countries.
Trial summary
The purpose of this study is to evaluate the efficacy of loncastuximab tesirine (ADCT-402) combined with rituximab compared to standard immunochemotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed Diffuse Large B-Cell Lymphoma, Refractory Diffuse Large B-Cell Lymphoma
- What is being tested?
- Loncastuximab Tesirine, Rituximab and Gemcitabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 440 participants
- Where
- 144 sitesin 21 countries
- Study dates
- 16 Sep 2020to 30 Jun 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 participant aged 18 years or older
- Pathologic diagnosis of DLBCL, as defined by the 2016 World Health Organization classification (including participants with DLBCL transformed from indolent lymphoma), or high-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements
- Relapsed (disease that has recurred following a response) or refractory (disease that failed to respond to prior therapy) disease following at least one multi-agent systemic treatment regimen [For China only: Adequate first line anti-DLBCL therapy is defined as having received at least 4 cycles of multiagent systemic treatment regimen containing rituximab and anthracycline, unless the participants are intolerant to the regimen, or had disease progression during the treatment. If disease progression occurred during the treatment period, then the disease is considered refractory where the number of treatment cycles will not be specified. For participants who are ineligible for anthracycline, anthracycline is not required.]
- Not considered by the investigator to be a candidate for stem cell transplantation based on performance status, advanced age, and/or significant medical comorbidities such as organ dysfunction
- Measurable disease as defined by the 2014 Lugano Classification as assessed by positron-emission tomography (PET)- computed tomography (CT) or by CT or magnetic resonance imaging (MRI) if tumor is not fluorodeoxyglucose (FDG)-avid on screening PET-CT
- Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block (or minimum 10 freshly cut unstained slides if block is not available) Note: Any biopsy since initial diagnosis is acceptable, but if several samples are available, the most recent sample is preferred [For China only: This inclusion criterion is not applicable]
Show all 16Show fewer
- ECOG performance status 0-2
- Adequate organ function as defined by screening laboratory values within the following parameters:
- Absolute neutrophil count ≥1000/μL (off growth factors for at least 72 hours)
- Platelet count ≥100000/μL without transfusion within the past 2 weeks
- ALT, AST, and GGT ≤2.5 × the upper limit of normal (ULN)
- Total bilirubin ≤1.5 × ULN (participants with known Gilbert's syndrome may have a total bilirubin up to ≤3 × ULN)
- Calculated creatinine clearance ≥30 mL/min by the Cockcroft and 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 (Cycle 1 Day 1) 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 12 months after the last dose of study treatment. 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 until at least 7 months after the participant receives his last dose of study treatment.
Who cannot join
- Previous treatment with loncastuximab tesirine
- Previous treatment with R-GemOx
- Known history of hypersensitivity to a CD19 antibody, loncastumiximab tesirine (including SG3249) or any of its excipients, or history of 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 transplant within 30 days prior to start of study drug (Cycle 1 Day 1)
Show all 29Show fewer
- Allogeneic transplant within 60 days prior to start of study drug (Cycle 1 Day 1)
- Active graft-versus-host disease
- Post-transplantation lymphoproliferative disorders
- Active autoimmune disease, including motor neuropathy considered of autoimmune origin and other central nervous system (CNS) autoimmune disease
- Human immunodeficiency virus (HIV) seropositive with any of the following:
- CD4+ T-cell (CD4+) counts <350 cells/μL
- Acquired immunodeficiency syndrome-defining opportunistic infection within 12 months prior to screening
- Not on anti-retroviral therapy, or on anti-retroviral therapy for <4 weeks at the time of screening
- HIV viral load ≥400 copies/mL
- 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 Stevens-Johnson syndrome or toxic epidermal necrolysis
- Lymphoma with active CNS 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
- Uncontrolled hypertension (blood pressure ≥160/100 mm Hg 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 6 months prior to screening, uncontrolled atrial or ventricular cardiac arrhythmia, poorly controlled diabetes, severe chronic pulmonary disease, or other serious medical condition which is likely to significantly impair the participant's ability to tolerate the study treatment
- Major surgery within 4 weeks prior to start of study drug (Cycle 1 Day 1); radiotherapy, chemotherapy or other antineoplastic therapy within 14 days prior to start of study drug (Cycle 1 Day 1), except shorter if approved by the Sponsor
- Use of any other experimental medication within 14 days or 5 half-lives prior to start of study drug (Cycle 1 Day 1)
- Received live vaccine within 4 weeks of Cycle 1 Day 1
- Failure to recover to ≤Grade 1 (Common Terminology Criteria for Adverse Events [CTCAE] version 5.0) from acute non-hematologic toxicity (except 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 participant inappropriate for study participation or put the participant at risk
- Known history of hypersensitivity to oxaliplatin or other platinum-based drugs, or gemcitabine, or rituximab, or any of their excipients
Trial locations and contacts
144 sites in 21 countries.
144 sites in 21 countries
Japan20 sites
Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital
Bunkyo-ku, Tokyo, 113-8677
Fukushima Medical University Hospital
Fukushima, 960-1295
Gifu Municipal Hospital
Gifu, 500-8323
Saitama Medical University - International Medical Center
Hidaka-Shi, Saitama, 350-1298
Kagoshima University Hospital
Kagoshima, 890-8520
National Cancer Center Hospital East
Kashiwa, Chiba, 277-8577
Kobe City Medical Center General Hospital
Kobe, Hyōgo, 650-0047
Matsuyama Red Cross Hospital
Matsuyama, Ehime, 790-8524
Nagasaki University Hospital
Nagasaki, Nagasaki, 852-8501
National Hospital Organization - Nagoya Medical Center
Nagoya, Aichi-ken, 460-0001
Niigata University Medical and Dental Hospital
Niigata, 951-8520
National Hospital Organization Okayama Medical Center
Okayama, 701-1192
Osaka Prefectural Hospital Organization - Osaka International Cancer Institute
Osaka, 541-8567
Gunma Prefectural Cancer Center
Ōta, Gunma, 373-8550
Sapporo Hokuyu Hospital
Sapporo, Hokkaido, 003-0006
Hokkaido Cancer Center
Sapporo, Hokkaido, 003-0804
Tohoku University Hospital
Sendai, Miyagi, 980-8574
National Hospital Organization Disaster Medical Center
Tachikawa, Tokyo, 190-0014
Toyohashi Municipal Hospital
Toyohashi, Aichi-ken, 441-8570
Kanagawa Cancer Center
Yokohama, Kanagawa, 241-8515
China19 sites
Peking University Third Hospital
Beijing, Beijing Municipality, 100191
Jilin Cancer Hospital
Changchun, Jilin, 130021
The First Hospital of Jilin University
Changchun, Jilin, 130021
West China School of Medicine - West China Hospital of Sichuan University
Chengdu, Sichuan, 610041
Chongqing University Cancer Hospital - Chongqing Cancer Hospital
Chongqing, 400030
Second Affiliated Hospital of Dalian Medical University
Dalian, Liaoning, 116000
Sun Yat-Sen University Cancer Center
Guangzhou, Guangdong, 510060
Guangdong Provincial People's Hospital
Guangzhou, Guangdong, 510080
Zhujiang Hospital of Southern Medical University
Guangzhou, Guangdong, 510280
The First Affiliated Hospital of Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310003
Huizhou Municipal Central Hospital
Huizhou, 516001
The First Affiliated Hospital of Nanchang University
Nanchang, 330006
Shanghai Cancer Center
Shanghai, Shanghai Municipality, 200025
Tianjin Medical University Cancer Institute & Hospital
Tianjin, Tianjin Municipality, 300060
Institute of Hematology and Blood Diseases Hospital of CAMS - PUMC
Tianjin, 300020
Wuhan Union Hospital
Wuhan, 430023
Tongji Hospital
Wuhan, 430030
The First Affiliated Hospital of Xiamen University
Xiamen, Fujian, 361001
Henan Cancer Hospital - Zhengzhou University
Zhengzhou, Henan, 450008
United States11 sites
Hollings Cancer Center
Charleston, South Carolina, 29425
UnityPoint Health - Iowa Oncology Research Association (IORA)
Des Moines, Iowa, 50309
Virginia Cancer Specialists
Gainesville, Virginia, 20155
Baptist MD Anderson Cancer Center
Jacksonville, Florida, 32207
University of California San Diego Moores Cancer Center
La Jolla, California, 92093
Comprehensive Cancer Centers of Nevada - Henderson
Las Vegas, Nevada, 89169
Norton Cancer Institute
Louisville, Kentucky, 40207
Medical College of Wisconsin Cancer Center Clinical Trials Office
Milwaukee, Wisconsin, 53226
Kaiser Permanente Interstate Medical Office Central
Portland, Oregon, 97227
Redlands Community Hospital
Redlands, California, 92373
The Oncology Institute of Hope and Innovation
Whittier, California, 90603
Brazil10 sites
Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer
Curitiba, Paraná, 81520-060
Hospital Moinhos de Vento
Porto Alegre, Rio Grande do Sul, 90035-001
Hospital de Clínicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90035-903
Hospital Mãe de Deus - Centro Integrado de Oncologia
Porto Alegre, Rio Grande do Sul, 90110-270
Hospital do Câncer
Rio de Janeiro, 20230-130
Hemomed Instituto de Oncologia e Hematologia
São Paulo, 01236-030
A Beneficência Portuguesa de São Paulo - Unidade Mirante
São Paulo, 01321-001
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
São Paulo, 05403-010
Hospital Israelita Albert Einstein
São Paulo, 05652-900
Hospital Santa Marcelina
São Paulo, 08270-120
Italy10 sites
Azienda Socio Sanitaria Territoriale (ASST) degli Spedali Civili di Brescia
Brescia, 25123
Azienda Ospedaliero - Universitaria Careggi
Florence, 50134
Ospedale Casa Sollievo della Sofferenza
Foggia, 71013
Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST
Meldola, 47014
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Istituto Clinico Humanitas
Milan, 20089
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale San Raffaele
Milan, 20132
Istituto Europeo di Oncologia
Milan, 20141
Fondazione IRCCS Policlinico San Matteo
Pavia, 27100
Sanitaria Locale della Romagna
Ravenna, 48121
Presidio Ospedaliero Universitario Santa Maria della Misericordia
Udine, Friuli Venezia Giulia, 33100
Spain10 sites
Hospital del Mar - Parc de Salut Mar
Barcelona, 08003
Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
Barcelona, 08908
Hospital San Pedro de Alcantara
Cáceres, 10003
Hospital Universitario Ramón y Cajal
Madrid, 28034
Hospital Universitario Fundación Jiménez Díaz
Madrid, 28040
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Universitario La Paz
Madrid, 28046
Hospital Universitario Marqués de Valdecilla
Santander, 39008
Hospital Universitario Virgen del Rocío
Seville, 41013
Hospital Arnau de Vilanova
Valencia, 25198
France8 sites
Hôpital Avicenne
Bobigny, 93000
Centre Hospitalier Regional Universitaire Brest
Brest, Brittany Region, 29200
Centre Hospitalier Regional Universitaire Brest
Brest, 29200
Hôpital François Mitterrand
Dijon, 21000
Hôpital Privé du Confluent
Nantes, 44200
Hopital Universitaire Pitie Salpetriere
Paris, 75651
Hôpital Haut-Lévêque
Pessac, 33604
Centre de Lutte Contre le Cancer - Centre Henri-Becquerel
Rouen, 76038
Poland8 sites
Szpitale Pomorskie Spółka Z Ograniczoną Odpowiedzialnością
Gdynia, 81-519
Pratia Onkologia Katowice
Katowice, 40-519
Pratia MCM Kraków
Krakow, Lesser Poland Voivodeship, 30-510
Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi
Lodz, 93-510
Szpital Wojewódzki w Opolu
Opole, 45-061
Centrum Medyczne Pratia Poznań
Skorzewo, 60-185
Instytut Hematologii I Transfuzjologii
Warsaw, 02-776
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu
Wroclaw, Lower Silesian Voivodeship, 50-367
Israel7 sites
Samson Assuta Ashdod University Hospital
Ashdod, 7747629
Shamir Medical Center (Assaf Harofeh)
Be’er Ya‘aqov, 7030000
Soroka Medical Center
Beersheba, 8410101
Carmel Medical Center
Haifa, 3436212
Rabin Medical Center - Beilinson Hospital
Petah Tikva, 4941492
The Chaim Sheba Medical Center
Tel Aviv, 52621
Tel Aviv Sourasky Medical Center
Tel Aviv, 6423906
Turkey (Türkiye)7 sites
Ankara Universitesi Tip Fakultesi - Cebeci Arastirma ve Uygulama Hastanesi
Ankara, 06100
Ege Universitesi Tip Fakultesi Hastanesi
Bornova, İzmir, 35100
Özel Koru Hastanesi
Çukurambar, Ankara, 6510
Mehmet Kemal Dedeman Hematoloji Hastanesi
Kayseri, 38039
Ondokuz Mayis Üniversitesi
Kurupelit, Samsun, 55270
Karadeniz Teknik Üniversitesi Tip Fakültesi
Ortahisar, Trabzon, 61080
VKV Amerikan Hastanesi
Şişli, Istanbul, 34365
Mexico6 sites
PanAmerican Clinical Research Mexico - Cuernavaca
Cuernavaca, Morelos, 62290
Boca Raton Clinical Research (BRCR) Global Mexico - Guadalajara
Guadalajara, Jalisco, 44600
PanAmerican Clinical Research Mexico - Guadalajara
Guadalajara, Jalisco, 44670
Hematológica Alta Especialidad
Huixquilucan, 52787
Boca Raton Clinical Research (BRCR) Global Mexico - Ciudad de México
Mexico City, 1120
Hospital Universitario Dr. José Eleuterio González
Monterrey, Nuevo León, 64460
Argentina4 sites
Clinica Adventista Belgrano
Belgrano, Buenos Aires, C1430EGF
Instituto Médico Especializado Alexander Fleming
Buenos Aires, Distrito Federal, C1426ANZ
Grupo Gamma - Hospital Privado Rosario
Rosario, Santa Fe Province, S2000GAP
Clínica de Nefrología, Urología y Enfermedades Cardiovasculares S.A.
Santa Fe, Buenos Aires, 3000
Belgium4 sites
Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan
Bruges, 8000
Cliniques Universitaires Saint-Luc
Brussels, 1200
Centre Hospitalier Universitaire Universite Catholique de Louvain
Namur, B-5530
Algemeen Ziekenhuis Delta - Campus Rumbeke
Roeselare, 8800
Hungary4 sites
Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet - Szent László
Budapest, Pest County, 1097
Semmelweis Egyetem
Budapest, 1088
Orszagos Onkologiai Intezet
Budapest, 1122
Heves Varmegyei Markhot Ferenc Oktatokorhaz es Rendelointezet
Heves, Budapest, 3300
Canada3 sites
Cross Cancer Institute
Edmonton, T6G 1Z2
Research Institute of the McGill University Health Centre
Montreal, H4A 3J1
Hôpital Fleurimont
Sherbrooke, J1H 5H3
Chile3 sites
Centro de Estudios Clínicos SAGA
Santiago, Santiago Metropolitan, 7500653
Instituto Oncológico Fundación Arturo López Pérez
Santiago, Santiago Metropolitan, 8320000
CeCim - Centro de Estudios Clínicos e Investigaciones Médicas
Santiago, Santiago Metropolitan, 8330109
Czechia3 sites
Fakultni nemocnice Ostrava
Ostrava, 708 52
Fakultni Nemocnice Kralovske Vinohrady
Prague, 100 34
Fakultni nemocnice v Motole
Prague, 150 06
United Kingdom3 sites
NHS Greater Glasgow and Clyde
Glasgow, G12 0XH
The Christie NHS Foundation Trust
Manchester, M20 4BX
The Royal Marsden NHS Foundation Trust
Sutton, England, SM2 5PT
Netherlands2 sites
Hagaziekenhuis Van Den Haag - Leyweg
The Hague, South Holland, 2545 AA
Elisabeth-TweeSteden Ziekenhuis - Elisabeth
Tilburg, 5022 GC
Switzerland1 site
Istituto Oncologico della Svizzera Italiana
Bellinzona, 6500
About this study
Official title: A Phase 3 Randomized Study of Loncastuximab Tesirine Combined With Rituximab Versus Immunochemotherapy in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) (LOTIS-5)
The purpose of this study is to evaluate the efficacy of loncastuximab tesirine (ADCT-402) combined with rituximab compared to standard immunochemotherapy.
- Being tested
- Loncastuximab Tesirine, Rituximab, Gemcitabine, Oxaliplatin
- Keywords
- Loncastuximab Tesirine, Refractory Diffuse Large B-Cell Lymphoma, Relapsed Diffuse Large B-Cell Lymphoma, Diffuse Large B-Cell Lymphoma, Lymphoma
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Lymphoma
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
RituximabDrug
Intravenous Infusion
GemcitabineDrug
Intravenous Infusion
OxaliplatinDrug
Intravenous Infusion
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Loncastuximab Tesirine + Rituximab (Lonca-R) | Experimental | Part 1 consists of a non-randomized safety run-in period evaluating the study drug for the first 20 participants.
Participants will receive Lonca-R on Day 1 of each cycle for up to 8 cycles, where 1 cycle is 3 weeks. Lonca-R will be administered via an intravenous infusion of loncastuximab tesirine 150 µg/kg + rituximab 375 mg/m^2 Q3W for 2 cycles, then loncastuximab tesirine 75 µg/kg + rituximab 375 mg/m^2 Q3W for up to 6 additional cycles. Receives: Drug: Loncastuximab Tesirine; Drug: Rituximab |
| Part 2: Loncastuximab Tesirine + Rituximab (Lonca-R) | Experimental | Randomized participants will receive Lonca-R on Day 1 of each cycle for up to 8 cycles, where 1 cycle is 3 weeks. Lonca-R will be administered via an intravenous infusion of loncastuximab tesirine 150 µg/kg + rituximab 375 mg/m^2 every Q3W for 2 cycles, then loncastuximab tesirine 75 µg/kg + rituximab 375 mg/m^2 Q3W for up to 6 additional cycles. Receives: Drug: Loncastuximab Tesirine; Drug: Rituximab |
| Part 2: Standard Immunochemotherapy (R-GemOx) | Active comparator | Randomized participants will receive R-GemOx consisting of rituximab, gemcitabine and oxaliplatin as a standard immunochemotherapy treatment on Day 1 or Day 2 of each cycle for up to 8 cycles, where 1 Cycle is 2 weeks. R-GemOx will be administered via an intravenous infusion of rituximab 375 mg/m^2 + gemcitabine 1000 mg/m^2 + oxaliplatin 100 mg/m^2 every 2 weeks (Q2W) for up to 8 cycles. Receives: Drug: Rituximab; Drug: Gemcitabine; Drug: Oxaliplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS)
Measured: Up to 4 years
Secondary outcomes (18)
Overall Survival (OS)
Measured: Up to 4 years
Overall Response Rate (ORR)
Measured: Up to 4 years
Complete Response Rate (CRR)
Measured: Up to 4 years
Duration of Response (DOR)
Measured: Up to 4 years
Number of Participants Who Experience At Least One Treatment-Emergent Adverse Event (TEAE)
Measured: Day 1 up to a maximum of Week 39
Number of Participants Who Experience At Least One Serious Adverse Event (SAE)
Measured: Up to 4 years
Number of Participants Who Experience a Clinically Significant Change From Baseline in Clinical Laboratory Results
Measured: Day 1 up to a maximum of Week 25
Number of Participants Who Experience a Clinically Significant Change From Baseline in Vital Sign Measurements
Measured: Day 1 up to a maximum of Week 25
Number of Participants Who Experience a Clinically Significant Change From Baseline in Physical Examinations
Measured: Day 1 up to a maximum of Week 25
Number of Participants Who Experience a Clinically Significant Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status
Measured: Day 1 up to a maximum of Week 25
Number of Participants Who Experience a Clinically Significant Change From Baseline in Electrocardiogram (ECG) Results
Measured: Day 1 up to a maximum of Week 25
Average Concentration of Loncastuximab Tesirine at the End of Infusion
Measured: Day 1 of Cycles 1 through 6 (each cycle is 3 weeks)
Average Concentration of Loncastuximab Tesirine Before Infusion
Measured: Day 1 of Cycles 1 through 6 (each cycle is 3 weeks)
Number of Participants With Anti-Drug Antibody (ADA) Titers to Loncastuximab Tesirine
Measured: Day 1 up to a maximum of Week 25
Part 2: Change from Baseline in Health-Related Quality of Life (HRQoL) as Measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire -Core 30 (EORTC QLQ-C30)
Measured: Baseline up to a maximum of Week 25
Part 2: Change from Baseline in Health-Related Quality of Life (HRQoL) as Measured by the Lymphoma Subscale of Functional Assessment of Cancer Therapy- Lymphoma (LymS of FACT-Lym)
Measured: Baseline up to a maximum of Week 25
Part 2: Change from Baseline in Health-Related Quality of Life (HRQoL) as Measured by GP5 Item of the Functional Assessment of Cancer Therapy- Lymphoma (FACT-Lym)
Measured: Baseline up to a maximum of Week 25
Part 2: Change from Baseline in Health-Related Quality of Life (HRQoL) as Measured by EuroQol-5 Dimensions-5 Levels (EQ-5D-5L)
Measured: Baseline to up to 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2020
- Study start16 Sep 2020
- Primary completion31 Mar 2026
- Study completion30 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed Diffuse Large B-Cell LymphomaStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 440 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
- NCT04384484
- Sponsor's protocol ID
- ADCT-402-311
- Other IDs
- 2020-000241-14
- Acronym
- LOTIS 5
- Status last verified
- Apr 2026
- First submitted
- 8 May 2020
- Last updated
- 28 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3 Randomized Study of Loncastuximab Tesirine Combined With Rituximab Versus Immunochemotherapy in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) (LOTIS-5)
- ClinicalTrials.gov ID
- NCT04384484
- Acronym / sponsor ID
- LOTIS 5 / ADCT-402-311
- Keywords
- Loncastuximab Tesirine, Refractory Diffuse Large B-Cell Lymphoma, Relapsed Diffuse Large B-Cell Lymphoma, Diffuse Large B-Cell Lymphoma, Lymphoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 440 participants (actual)
- Lead sponsor
- ADC Therapeutics S.A.Industry (pharma, biotech, devices)
- Study start
- 16 Sep 2020 (actual)
- Primary completion
- 31 Mar 2026 (actual)
- Study completion
- 30 Jun 2028 (estimated)
- First posted
- 12 May 2020 (actual)
- Results
- Not posted in the source record
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 study is to evaluate the efficacy of loncastuximab tesirine (ADCT-402) combined with rituximab compared to standard immunochemotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part 1: Loncastuximab Tesirine + Rituximab (Lonca-R) | Experimental | Drug: Loncastuximab Tesirine, Drug: RituximabPart 1 consists of a non-randomized safety run-in period evaluating the study drug for the first 20 participants. Participants will receive Lonca-R on Day 1 of each cycle for up to 8 cycles, where 1 cycle is 3 weeks. Lonca-R will be administered via an intravenous infusion of loncastuximab tesirine 150 µg/kg + rituximab 375 mg/m^2 Q3W for 2 cycles, then loncastuximab tesirine 75 µg/kg + rituximab 375 mg/m^2 Q3W for up to 6 additional cycles. |
| Part 2: Loncastuximab Tesirine + Rituximab (Lonca-R) | Experimental | Drug: Loncastuximab Tesirine, Drug: RituximabRandomized participants will receive Lonca-R on Day 1 of each cycle for up to 8 cycles, where 1 cycle is 3 weeks. Lonca-R will be administered via an intravenous infusion of loncastuximab tesirine 150 µg/kg + rituximab 375 mg/m^2 every Q3W for 2 cycles, then loncastuximab tesirine 75 µg/kg + rituximab 375 mg/m^2 Q3W for up to 6 additional cycles. |
| Part 2: Standard Immunochemotherapy (R-GemOx) | Active comparator | Drug: Rituximab, Drug: Gemcitabine, Drug: OxaliplatinRandomized participants will receive R-GemOx consisting of rituximab, gemcitabine and oxaliplatin as a standard immunochemotherapy treatment on Day 1 or Day 2 of each cycle for up to 8 cycles, where 1 Cycle is 2 weeks. R-GemOx will be administered via an intravenous infusion of rituximab 375 mg/m^2 + gemcitabine 1000 mg/m^2 + oxaliplatin 100 mg/m^2 every 2 weeks (Q2W) for up to 8 cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Male or female participant aged 18 years or older
- Pathologic diagnosis of DLBCL, as defined by the 2016 World Health Organization classification (including participants with DLBCL transformed from indolent lymphoma), or high-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements
- Relapsed (disease that has recurred following a response) or refractory (disease that failed to respond to prior therapy) disease following at least one multi-agent systemic treatment regimen [For China only: Adequate first line anti-DLBCL therapy is defined as having received at least 4 cycles of multiagent systemic treatment regimen containing rituximab and anthracycline, unless the participants are intolerant to the regimen, or had disease progression during the treatment. If disease progression occurred during the treatment period, then the disease is considered refractory where the number of treatment cycles will not be specified. For participants who are ineligible for anthracycline, anthracycline is not required.]
- Not considered by the investigator to be a candidate for stem cell transplantation based on performance status, advanced age, and/or significant medical comorbidities such as organ dysfunction
- Measurable disease as defined by the 2014 Lugano Classification as assessed by positron-emission tomography (PET)- computed tomography (CT) or by CT or magnetic resonance imaging (MRI) if tumor is not fluorodeoxyglucose (FDG)-avid on screening PET-CT
Key exclusion criteria (29 listed)
- Previous treatment with loncastuximab tesirine
- Previous treatment with R-GemOx
- Known history of hypersensitivity to a CD19 antibody, loncastumiximab tesirine (including SG3249) or any of its excipients, or history of 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
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 | Part 1: Loncastuximab Tesirine + Rituximab (Lonca-R), Part 2: Loncastuximab Tesirine + Rituximab (Lonca-R) |
| RituximabIntravenous Infusion | Drug | Part 1: Loncastuximab Tesirine + Rituximab (Lonca-R), Part 2: Loncastuximab Tesirine + Rituximab (Lonca-R), Part 2: Standard Immunochemotherapy (R-GemOx) |
| GemcitabineIntravenous Infusion | Drug | Part 2: Standard Immunochemotherapy (R-GemOx) |
| OxaliplatinIntravenous Infusion | Drug | Part 2: Standard Immunochemotherapy (R-GemOx) |
Primary outcome
Progression-free Survival (PFS)
Time frame: Up to 4 years
18 secondary outcomes
Overall Survival (OS)
Time frame: Up to 4 years
Overall Response Rate (ORR)
Time frame: Up to 4 years
Complete Response Rate (CRR)
Time frame: Up to 4 years
Duration of Response (DOR)
Time frame: Up to 4 years
Number of Participants Who Experience At Least One Treatment-Emergent Adverse Event (TEAE)
Time frame: Day 1 up to a maximum of Week 39
Number of Participants Who Experience At Least One Serious Adverse Event (SAE)
Time frame: Up to 4 years
Number of Participants Who Experience a Clinically Significant Change From Baseline in Clinical Laboratory Results
Time frame: Day 1 up to a maximum of Week 25
Number of Participants Who Experience a Clinically Significant Change From Baseline in Vital Sign Measurements
Time frame: Day 1 up to a maximum of Week 25
Number of Participants Who Experience a Clinically Significant Change From Baseline in Physical Examinations
Time frame: Day 1 up to a maximum of Week 25
Number of Participants Who Experience a Clinically Significant Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status
Time frame: Day 1 up to a maximum of Week 25
Number of Participants Who Experience a Clinically Significant Change From Baseline in Electrocardiogram (ECG) Results
Time frame: Day 1 up to a maximum of Week 25
Average Concentration of Loncastuximab Tesirine at the End of Infusion
Time frame: Day 1 of Cycles 1 through 6 (each cycle is 3 weeks)
Average Concentration of Loncastuximab Tesirine Before Infusion
Time frame: Day 1 of Cycles 1 through 6 (each cycle is 3 weeks)
Number of Participants With Anti-Drug Antibody (ADA) Titers to Loncastuximab Tesirine
Time frame: Day 1 up to a maximum of Week 25
Part 2: Change from Baseline in Health-Related Quality of Life (HRQoL) as Measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire -Core 30 (EORTC QLQ-C30)
Time frame: Baseline up to a maximum of Week 25
Part 2: Change from Baseline in Health-Related Quality of Life (HRQoL) as Measured by the Lymphoma Subscale of Functional Assessment of Cancer Therapy- Lymphoma (LymS of FACT-Lym)
Time frame: Baseline up to a maximum of Week 25
Part 2: Change from Baseline in Health-Related Quality of Life (HRQoL) as Measured by GP5 Item of the Functional Assessment of Cancer Therapy- Lymphoma (FACT-Lym)
Time frame: Baseline up to a maximum of Week 25
Part 2: Change from Baseline in Health-Related Quality of Life (HRQoL) as Measured by EuroQol-5 Dimensions-5 Levels (EQ-5D-5L)
Time frame: Baseline to up to 4 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2026.
- Individual participant dataSharing planned: No
Related trials for Relapsed Diffuse Large B-Cell Lymphoma
Active, not recruitingEarly Phase 1
Iomab-ACT: A Pilot Study of 131-I Apamistamab Followed by CD19-Targeted CAR T-Cell Therapy for Patients With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia or Diffuse Large B-Cell Lymphoma
B-ALL, DLBCL
RecruitingPhase 2
Testing the Effectiveness of a Combination Targeted Therapy (ViPOR) for Patients With Relapsed and/or Refractory Aggressive B-cell Lymphoma
High Grade B-Cell Lymphoma With MYC and BCL6 Rearrangements, Recurrent Diffuse Large B-Cell Lymphoma
RecruitingPhase 1/2
Dose Escalation and Dose Expansion Study of MDX2003 in Patients With Different Types of Lymphoma
Lymphoma, Waldenström Macroglobulinemia (WM)
RecruitingPhase 1/2
Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (ViPOR) in Relapsed/Refractory B-cell Lymphoma
Lymphoma, Non-Hodgkin Lymphoma
Not yet recruitingPhase 2/3
A Clinical Trial of MK-1045 With Zilovertamab Vedotin in Participants With Diffuse Large B-cell Lymphoma (MK-1045-010)
Lymphoma, Large B-Cell, Diffuse, Diffuse Large B-Cell Lymphoma
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.
144 sites in 21 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Loncastuximab Tesirine, Rituximab and Gemcitabine in people with Relapsed Diffuse Large B-Cell Lymphoma and Refractory Diffuse Large B-Cell Lymphoma, run by ADC Therapeutics S.A. at 144 sites in 21 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 16 inclusion and 29 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: under way, not looking for participants, as of the sponsor's last update on 28 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 144 sites in Japan, China, United States, Brazil, Italy and 16 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Progression-free Survival (PFS) (time frame: Up to 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Apr 2026.