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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

ADC Therapeutics S.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

24 Mar 2021 → ongoing

Decision date (initial)

2024-03-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

ADC Therapeutics SA

External identifiers

EU CT number

2023-503916-33-00

EudraCT number

2020-000241-14

ClinicalTrials.gov

NCT04384484

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Therapy, Pharmacokinetic, Pharmacogenetic, Efficacy, Safety

Evaluate the efficacy of loncastuximab tesirine combined with rituximab compared to standard immunochemotherapy compared to standard immunochemotherapy

Conditions and MedDRA coding

Diffuse Large B-Cell Lymphoma (DLBCL)

Study design 4 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Male or female patient aged 18 years or older
2. Pathologic diagnosis of DLBCL, as defined by the 2016 World Health Organization classification (including patients with DLBCL transformed from indolent lymphoma), or high-grade B cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements
3. 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
4. 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
5. 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
6. 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.
7. ECOG performance status 0-2
8. Adequate organ function as defined by screening laboratory values within the following parameters: a. Absolute neutrophil count ≥1000/µL (off growth factors at least 72 hours) b. Platelet count ≥100000/µL without transfusion within the past 2 weeks c. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) ≤2.5 × the upper limit of normal (ULN) d. Total bilirubin ≤1.5 × ULN (patients with known Gilbert's syndrome may have a total bilirubin up to ≤3 × ULN) e. 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.
9. 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
10. 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 patient receives his last dose of study treatment.

Exclusion criteria 25

1. Previous treatment with loncastuximab tesirine
2. Previous treatment with R-GemOx
3. Known history of hypersensitivity to a CD19 antibody, loncastuximab tesirine (including SG3249) or any of its excipients, or history of or positive serum human ADA to a CD19 antibody
4. Pathologic diagnosis of Burkitt lymphoma
5. 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
6. Autologous transplant within 30 days prior to start of study drug (Cycle 1 Day 1)
7. Allogeneic transplant within 60 days prior to start of study drug (Cycle 1 Day 1)
8. Active graft-versus-host disease
9. Post-transplantation lymphoproliferative disorders
10. Active autoimmune disease, including motor neuropathy considered of autoimmune origin and other central nervous system (CNS) autoimmune disease
11. Human immunodeficiency virus (HIV) seropositive with any of the following: a. CD4+ T-cell (CD4+) counts <350 cells/µL b. Acquired immunodeficiency syndrome-defining opportunistic infection within 12 months prior to screening c. Not on anti-retroviral therapy, or on anti-retroviral therapy for <4 weeks at the time of screening d. HIV viral load ≥400 copies/mL
12. 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
13. Serologic evidence of hepatitis C virus (HCV) infection without completion of curative treatment or with detectable HCV viral load
14. History of Stevens-Johnson syndrome or toxic epidermal necrolysis
15. Lymphoma with active CNS involvement, including leptomeningeal disease
16. 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)
17. Breastfeeding or pregnant
18. 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 patient's ability to tolerate the study treatment
19. 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
20. Use of any other experimental medication within 14 days or 5 half- lives prior to start of study drug (Cycle 1 Day 1)
21. Received live vaccine within 4 weeks of Cycle 1 Day 1
22. 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
23. Congenital long QT syndrome or a corrected QTcF interval of ≥480 ms at screening (unless secondary to pacemaker or bundle branch block)
24. 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
25. Known history of hypersensitivity to oxaliplatin or other platinum- based drugs, or gemcitabine, or rituximab, or any of their excipients

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival (PFS) defined as the time between randomization and the first documentation of recurrence or progression by independent central review, or death from any cause

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Comparator 2

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

ADC Therapeutics S.A.

Sponsor organisation

ADC Therapeutics S.A.

Address

Route De La Corniche 3b

City

Epalinges

Postcode

1066

Country

Switzerland

Scientific contact point

Organisation

ADC Therapeutics S.A.

Contact name

ADC Therapeutics SA

Public contact point

Organisation

ADC Therapeutics S.A.

Contact name

ADC Therapeutics SA

Third parties 13

Locations

8 EU/EEA countries · 43 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 62 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications