Study to evaluate loncastuximab tesirina in combination with rituximab compared to immunochemotherapy in participants with relapsed or refractory diffuse large B-cell lymphoma (LOTIS-5)

Argentina, Belgium, Brazil, Canada, Chile, China, Czechia, France, Hungary, Israel, Italy, Japan, Mexico, Netherlands, Poland, Puerto Rico, Spain, Switzerland, Turkey (T�rkiye), United Kingdom, United States (ICTRP)

ID di studio ICTRP
NCT04384484 (ICTRP)

Titolo ufficiale (approvato dal comitato etico)
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) (BASEC)

Titolo accademico
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) (ICTRP)

Titolo pubblico
Study to Evaluate Loncastuximab Tesirine With Rituximab Versus Immunochemotherapy in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (ICTRP)

Malattie studiate
Relapsed Diffuse Large B-Cell LymphomaRefractory Diffuse Large B-Cell Lymphoma (ICTRP)

Intervento studiato
Drug: Loncastuximab TesirineDrug: RituximabDrug: GemcitabineDrug: Oxaliplatin (ICTRP)

Tipo di studio
Interventional (ICTRP)

Disegno dello studio
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Criteri di inclusione/esclusione
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 [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]

- ECOG performance status 0-2

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

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

2. Platelet count =100000/L 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 (-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.

Exclusion Criteria:

- 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)

- 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/L

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 (ICTRP)

non disponibile

Endpoint primari e secondari
Progression-free Survival (PFS) (ICTRP)

Overall Survival (OS);Overall Response Rate (ORR);Complete Response Rate (CRR);Duration of Response (DOR);Number of Participants Who Experience At Least One Treatment-Emergent Adverse Event (TEAE);Number of Participants Who Experience At Least One Serious Adverse Event (SAE);Number of Participants Who Experience a Clinically Significant Change From Baseline in Clinical Laboratory Results;Number of Participants Who Experience a Clinically Significant Change From Baseline in Vital Sign Measurements;Number of Participants Who Experience a Clinically Significant Change From Baseline in Physical Examinations;Number of Participants Who Experience a Clinically Significant Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status;Number of Participants Who Experience a Clinically Significant Change From Baseline in Electrocardiogram (ECG) Results;Average Concentration of Loncastuximab Tesirine at the End of Infusion;Average Concentration of Loncastuximab Tesirine Before Infusion;Number of Participants With Anti-Drug Antibody (ADA) Titers to Loncastuximab Tesirine;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);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);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);Part 2: Change from Baseline in Health-Related Quality of Life (HRQoL) as Measured by EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) (ICTRP)

Data di registrazione
non disponibile

Inclusione del primo partecipante
non disponibile

Sponsor secondari
non disponibile

Contatti aggiuntivi
ADC Therapeutics, clinical.trials@adctherapeutics.com, 954-903-7994 (ICTRP)

ID secondari
2020-000241-14, ADCT-402-311 (ICTRP)

Risultati-Dati individuali dei partecipanti
non disponibile

Ulteriori informazioni sullo studio
https://clinicaltrials.gov/study/NCT04384484 (ICTRP)