Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL) MedDRA version: 20.0 Level: PT Classification code 10012818 Term: Diffuse large B-cell lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Loncastuximab Tesirine
Product Code: ADCT-402
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Loncastuximab Tesirine
Current Sponsor code: ADCT-402
Concentration unit: mg
Sponsors
ADC THERAPEUTICS SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patient aged 18 years or older 2. 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 3. Relapsed or refractory disease following two or more multi-agent systemic treatment regimens 4. Patients who have received previous CD19-directed therapy must have a biopsy that shows CD19 protein expression after completion of the CD19-directed therapy 5. Measurable disease as defined by the 2014 Lugano Classification 6. Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block (or minimum 10 freshly cut unstained slides if block is not available) 7. ECOG performance status 0-2 8. Adequate organ function as defined by screening laboratory values within the following parameters: a. Absolute neutrophil count (ANC) =1.0 × 10^3/µL (off growth factors at least 72 hours) b. Platelet count =75 × 10^3/µL without transfusion in the prior 7 days c. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) =2.5 × the upper limit of normal (ULN); =5 × ULN if there is liver involvement d. Total bilirubin =1.5 × ULN (patients with known Gilbert’s syndrome may have a total bilirubin up to =3 × ULN) e. Blood creatinine =1.5 × ULN or calculated creatinine clearance =60 mL/min by the Cockcroft and Gault equation 9. Negative beta-human chorionic gonadotropin (ß-HCG) pregnancy test within 7 days prior to start of study drug (C1D1) 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 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 Are the trial subjects under 18? no Number of subjects for this age range: 1 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 42 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 98
Exclusion criteria
Exclusion criteria: 1. Previous treatment with loncastuximab tesirine 2. Known history of hypersensitivity to or positive serum human ADA to a CD19 antibody 3. Pathologic diagnosis of Burkitt lymphoma 4. 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 5. Autologous stem cell transplant within 30 days prior to start of study drug (C1D1) 6. Allogeneic stem cell transplant within 60 days prior to start of study drug (C1D1) 7. Active graft-versus-host disease 8. Post-transplant lymphoproliferative disorders 9. Active autoimmune disease, including motor neuropathy considered of autoimmune origin and other central nervous system (CNS) autoimmune disease 10. Known seropositive and requiring anti-viral therapy for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). 11. History of Stevens-Johnson syndrome or toxic epidermal necrolysis 12. Lymphoma with active CNS involvement at the time of screening, including leptomeningeal disease 13. 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) 14. Breastfeeding or pregnant 15. Significant medical comorbidities, including but not limited to, uncontrolled hypertension (blood pressure [BP] =160/100 mmHg 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, or severe chronic pulmonary disease 16. 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 17. Use of any other experimental medication within 14 days prior to start of study drug (C1D1) 18. Planned live vaccine administration after starting study drug (C1D1) 19. Failure to recover to Grade =1 (Common Terminology Criteria for Adverse Events [CTCAE] version 4.0) from acute non-hematologic toxicity (Grade =2 neuropathy or alopecia) due to previous therapy prior to screening 20. Congenital long QT syndrome or a corrected QTcF interval of >480 ms at screening (unless secondary to pacemaker or bundle branch block) 21. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the efficacy of single agent loncastuximab tesirine in patients with relapsed or refractory DLBCL;Secondary Objective: Characterize the safety profile of loncastuximab tesirine Characterize the pharmacokinetic (PK) profile of loncastuximab tesirine Evaluate the immunogenicity of loncastuximab tesirine Evaluate the impact of loncastuximab tesirine treatment on health-related quality of life (HRQoL) ;Primary end point(s): ORR according to the 2014 Lugano classification as determined by central review in all treated patients; ORR is defined as the proportion of patients with a best overall response (BOR) of CR or PR;Timepoint(s) of evaluation of this end point: Primary end point evaluated at 6 and 12 weeks after first dose, then every 9 weeks until disease progression. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): For further evaluation of efficacy of loncastuximab tesirine: - DOR defined as the time from the first documentation of tumor response to disease progression or death - CR rate defined as the percentage of treated patients with a BOR of CR - Relapse-free survival (RFS) defined as the time from the documentation of CR to disease progression or death - PFS defined as the time between start of treatment and the first documentation of recurrence, progression, or death - OS defined as the time between the start of treatment and death from any cause For characterization of safety profile of loncastuximab tesirine: - Frequency and severity of adverse events (AEs), and SAEs - Changes from baseline of safety laboratory variables, vital signs, ECOG performance status, and 12-lead electrocardiograms (ECGs) For characterization of PK profile of loncastuximab tesirine: - Concentrations and PK parameters of loncastuximab tesirine total antibody, PBD conjugated antibody, and unconjugated warhead SG3199 For evaluation of immunogenicity of loncastuximab tesirine: - Anti-drug antibody (ADA) titers and, if applicable, neutralizing activity to loncastuximab tesirine after treatment with loncastuximab tesirine For evaluation of impact of loncastuximab tesirine treatment on healthrelated quality of life (HRQoL): - Change from baseline in HRQoL as measured by EuroQol–5 Dimensions–5 Levels (EQ-5D-5L) and Functional Assessment of Cancer Therapy - Lymphoma (FACT Lym);Timepoint(s) of evaluation of this end point: There are different timepoints for evaluation of secondary end-points | — |
Countries
Italy, Switzerland, United Kingdom, United States
Contacts
Public ContactClinical Trials Information
ADC Therapeutics SA
Outcome results
None listed