LOTIS 5: Study to Evaluate Loncastuximab Tesirine With Rituximab Versus Immunochemotherapy in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

• Sponsor: ADC Therapeutics S.A. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04384484
• Collaborator: (none)
• Enrollment: 350
• Locations: 64
• Arms: 3
• Anticipated Duration (Months): 93.4
• Patients Per Site: 5.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy of loncastuximab tesirine (ADCT-402) combined with rituximab compared to standard immunochemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Relapsed Diffuse Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma	Drug: Loncastuximab Tesirine; Drug: Rituximab; Drug: Gemcitabine; Drug: Oxaliplatin	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 350 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: Sep 16, 2020
• Anticipated Primary Completion Date: Jun 30, 2025
• Anticipated Study Completion Date: Jun 30, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1: Loncastuximab Tesirine + Rituximab (Lonca-R) 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.	Drug: Loncastuximab Tesirine; Intravenous Infusion; Other Names: Zynlonta ADCT-402 ; Drug: Rituximab; Intravenous Infusion
Experimental: Part 2: Loncastuximab Tesirine + Rituximab (Lonca-R) 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.	Drug: Loncastuximab Tesirine; Intravenous Infusion; Other Names: Zynlonta ADCT-402 ; Drug: Rituximab; Intravenous Infusion
Active Comparator: Part 2: Standard Immunochemotherapy (R-GemOx) Randomized participants will receive R-GemOx consisting of rituximab, gemcitabine and oxaliplatin as a standard immunochemotherapy treatment on Day 1 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.	Drug: Rituximab; Intravenous Infusion; Drug: Gemcitabine; Intravenous Infusion; Drug: Oxaliplatin; Intravenous Infusion

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) [Up to 4 years]

Secondary Outcome Measures

1. Overall Survival (OS) [Up to 4 years]

2. Overall Response Rate (ORR) [Up to 4 years]

3. Complete Response Rate (CRR) [Up to 4 years]

4. Duration of Response (DOR) [Up to 4 years]

5. Number of Participants Who Experience At Least One Treatment-Emergent Adverse Event (TEAE) [Day 1 up to a maximum of Week 25]

6. Number of Participants Who Experience At Least One Serious Adverse Event (SAE) [Up to 4 years]

7. Number of Participants Who Experience a Clinically Significant Change From Baseline in Clinical Laboratory Results [Day 1 up to a maximum of Week 25]

8. Number of Participants Who Experience a Clinically Significant Change From Baseline in Vital Sign Measurements [Day 1 up to a maximum of Week 25]

9. Number of Participants Who Experience a Clinically Significant Change From Baseline in Physical Examinations [Day 1 up to a maximum of Week 25]

10. Number of Participants Who Experience a Clinically Significant Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status [Day 1 up to a maximum of Week 25]

11. Number of Participants Who Experience a Clinically Significant Change From Baseline in Electrocardiogram (ECG) Results [Day 1 up to a maximum of Week 25]

12. Average Concentration of Loncastuximab Tesirine at the End of Infusion [Day 1 of Cycles 1 through 6 (each cycle is 3 weeks)]

13. Average Concentration of Loncastuximab Tesirine Before Infusion [Day 1 of Cycles 2 through 6 (each cycle is 3 weeks)]

14. Number of Participants With Anti-Drug Antibody (ADA) Titers to Loncastuximab Tesirine [Day 1 up to a maximum of Week 25]

15. 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) [Baseline up to a maximum of Week 25]

16. 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) [Baseline up to a maximum of Week 25]

17. 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) [Baseline up to a maximum of Week 25]

18. Part 2: Change from Baseline in Health-Related Quality of Life (HRQoL) as Measured by EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) [Baseline to up to 4 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 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

• 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

• Participants who have received previous CD19-directed therapy must have a biopsy which shows CD19 expression after completion of the CD19-directed therapy

• 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

• ECOG performance status 0-2

• Adequate organ function as defined by screening laboratory values within the following parameters:

1. Absolute neutrophil count ≥1000/μL (off growth factors for at least 72 hours)

2. Platelet count ≥100000/μL without transfusion within the past 2 weeks

3. ALT, AST, and GGT ≤2.5 × the upper limit of normal (ULN)

4. Total bilirubin ≤1.5 × ULN (participants with known Gilbert's syndrome may have a total bilirubin up to ≤3 × ULN)

5. 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 6 months after the participant receives his last dose of study treatment.

Exclusion Criteria:

• Previous treatment with loncastuximab tesirine

• Previous treatment with R-GemOx

• 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 transplant within 30 days prior to start of study drug (Cycle 1 Day 1)

• 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:

1. CD4+ T-cell (CD4+) counts <350 cells/μL

2. Acquired immunodeficiency syndrome-defining opportunistic infection within 12 months prior to screening

3. Not on anti-retroviral therapy, or on anti-retroviral therapy for <4 weeks at the time of screening

4. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California San Diego Moores Cancer Center	La Jolla	California	United States	92093
2	Redlands Community Hospital	Redlands	California	United States	92373
3	The Oncology Institute of Hope and Innovation	Whittier	California	United States	90603
4	Baptist MD Anderson Cancer Center	Jacksonville	Florida	United States	32207
5	Miami Cancer Institute	Miami	Florida	United States	33176
6	Norton Cancer Institute	Louisville	Kentucky	United States	40207
7	University of Maryland Medical Center	Baltimore	Maryland	United States	21201
8	Comprehensive Cancer Centers of Nevada - Henderson	Las Vegas	Nevada	United States	89169
9	Kaiser Permanente Interstate Medical Office Central	Portland	Oregon	United States	97227
10	Hollings Cancer Center	Charleston	South Carolina	United States	29425
11	Texas Oncology Corporate Office	Dallas	Texas	United States	75251
12	Huntsman Cancer Institute and Hospital	Salt Lake City	Utah	United States	841112
13	Virginia Cancer Specialists	Gainesville	Virginia	United States	20155
14	Medical College of Wisconsin Cancer Center Clinical Trials Office	Milwaukee	Wisconsin	United States	53226
15	Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan	Brugge		Belgium	8000
16	Cliniques Universitaires Saint-Luc	Brussels		Belgium	1200
17	Centre Hospitalier Universitaire Universite Catholique de Louvain	Namur		Belgium	B-5530
18	Algemeen Ziekenhuis Delta - Campus Rumbeke	Roeselare		Belgium	8800
19	Cross Cancer Institute	Edmonton		Canada	T6G 1Z2
20	Research Institute of the McGill University Health Centre	Montréal		Canada	H4A 3J1
21	Hôpital Fleurimont	Sherbrooke		Canada	J1H 5H3
22	Huizhou Municipal Central Hospital	Huizhou		China	516001
23	The First Affiliated Hospital of Nanchang University	Nanchang		China	330006
24	Institute of Hematology and Blood Diseases Hospital of CAMS - PUMC	Tianjin		China	300020
25	Wuhan Union Hospital	Wuhan		China	430023
26	Tongji Hospital	Wuhan		China	430030
27	Fakultni nemocnice Ostrava	Ostrava		Czechia	708 52
28	Fakultni Nemocnice Kralovske Vinohrady	Prague		Czechia	100 34
29	Fakultni nemocnice v Motole	Prague		Czechia	150 06
30	Hôpital Avicenne	Bobigny		France	93000
31	Centre Hospitalier Regional Universitaire Brest	Brest		France	29200
32	CHU Dijon Bourgogne - Hôpital François Mitterrand	Dijon		France	21000
33	Hôpital Privé du Confluent	Nantes		France	44200
34	Hopital Universitaire Pitie Salpetriere	Paris		France	75651
35	Hôpital Haut-Lévêque	Pessac		France	33604
36	Centre de Lutte Contre le Cancer - Centre Henri-Becquerel	Rouen		France	76038
37	Samson Assuta Ashdod University Hospital	Ashdod		Israel	7747629
38	Soroka Medical Center	Be'er Sheva		Israel	8410101
39	Shamir Medical Center (Assaf Harofeh)	Be'er Ya'aqov		Israel	7030000
40	Carmel Medical Center	Haifa		Israel	3436212
41	Rabin Medical Center - Beilinson Hospital	Petah tikva		Israel	4941492
42	The Chaim Sheba Medical Center	Tel Aviv		Israel	52621
43	Tel Aviv Sourasky Medical Center	Tel Aviv		Israel	6423906
44	Azienda Socio Sanitaria Territoriale (ASST) degli Spedali Civili di Brescia	Brescia		Italy	25123
45	Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Istituto Clinico Humanitas	Milan		Italy	20089
46	Szpitale Pomorskie Spółka Z Ograniczoną Odpowiedzialnością	Gdynia		Poland	81-519
47	Pratia Onkologia Katowice	Katowice		Poland	40-519
48	Szpital Wojewódzki w Opolu	Opole		Poland	45-061
49	Centrum Medyczne Pratia Poznań	Skorzewo		Poland	60-185
50	Instytut Hematologii I Transfuzjologii	Warszawa		Poland	02-776
51	Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi	Łódź		Poland	93-510
52	Hospital del Mar - Parc de Salut Mar	Barcelona		Spain	08003
53	Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)	Barcelona		Spain	08908
54	Juan Miguel Bergua Burgues	Cáceres		Spain	10003
55	Hospital Universitario Ramón y Cajal	Madrid		Spain	28034
56	Hospital Universitario Fundación Jiménez Díaz	Madrid		Spain	28040
57	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
58	Hospital Universitario La Paz	Madrid		Spain	28046
59	Hospital Universitario Marqués de Valdecilla	Santander		Spain	39008
60	Hospital Universitario Virgen del Rocío	Sevilla		Spain	41013
61	Hospital Arnau de Vilanova	Valencia		Spain	25198
62	Istituto Oncologico della Svizzera Italiana	Bellinzona		Switzerland	6500
63	NHS Greater Glasgow and Clyde	Glasgow		United Kingdom	G12 0XH
64	The Christie NHS Foundation Trust	Manchester		United Kingdom	M20 4BX

Sponsors and Collaborators

• ADC Therapeutics S.A.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: ADC Therapeutics S.A.
• ClinicalTrials.gov Identifier: NCT04384484
• Other Study ID Numbers: ADCT-402-311; 2020-000241-14
• First Posted: May 12, 2020
• Last Update Posted: Aug 25, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by ADC Therapeutics S.A.: Loncastuximab Tesirine; Refractory Diffuse Large B-Cell Lymphoma; Relapsed Diffuse Large B-Cell Lymphoma; Diffuse Large B-Cell Lymphoma; Lymphoma
• Additional relevant MeSH terms: Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Gemcitabine; Rituximab; Loncastuximab tesirine; Oxaliplatin

Study Results

No Results Posted as of Aug 25, 2022