A Phase 3 Trial of Epcoritamab vs Investigator's Choice Chemotherapy in R/R DLBCL

JRCT ID: jRCT2021220017

Registered date:25/07/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Relapsed/Refractory DLBCL, who have failed or are ineligible for HDT-ASCT
• Date of first enrollment: 24/08/2021
• Target sample size: 50
• Countries of recruitment: France,Japan,Spain,Japan,Korea,Japan,Belgium,Japan,United Kingdom,Japan,Turkey,Japan,Hungary,Japan,Poland,Japan,Australia,Japan,Denmark,Japan,Italy,Japan,Norway,Japan,United States,Japan,Singapore,Japan,Russia,Japan,Finland,Japan,Netherlands,Japan,Israel,Japan,Sweden,Japan,Austria,Japan,Canada,Japan,Germany,Japan,Israel,Japan,Taiwan,Japan
• Study type: Interventional

Intervention(s)

Epcoritamab will be administered in Cycles of 28 days until any of the discontinuation criteria is met.
Investigator's choice will be one of the following:
R-GemOx (rituximab, gemcitabine and oxaliplatin) will be administrated in Cycles of 28 days until maximum cycles completion or any of the discontinuation criteria is met.
BR (bendamustine and rituximab) will be administrated in Cycles of 21 days until maximum cycles completion or any of the discontinuation criteria is met.

Outcome(s)

• Primary Outcome: Overall survival

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

-Must be at least 18 years of age;
-Subject (or their legally acceptable representative) must sign an informed consent form (ICF) indicating that the purpose of the trial and the procedures required for the trial are understood, and indicating that the subject is willing to participate in the trial prior to initiating any other trial-related assessments or procedures;
-ECOG PS score of 0-2;
-One of the confirmed histologies below with CD20-positivity:
* DLBCL, NOS (according to the WHO 2016 classification), including de novo or histologically transformed from follicular lymphoma (FL);
* "Double-hit" or "triple-hit" DLBCL (technically classified in WHO 2016 as HGBCL, with MYC and BCL2 and/or BCL6 translocations), including de novo or histologically transformed from FL
* Note: other double-/triple-hit lymphomas and those classified in WHO 2016 as HGBCL, NOS are not eligible;
* FL Grade 3B;
* T-cell/histiocyte-rich large B-cell lymphoma;
-CD20-positivity at representative (previous or current) tumor biopsy based on the pathology report;
-Relapsed or refractory disease and previously treated with at least 1 line of systemic antineoplastic therapy including anti-CD20 mAb-containing combination chemotherapy since lymphoma diagnosis (ie, having received R-CHOP or an equivalent regimen that would be considered adequate first-line treatment for DLBCL);
* Relapsed disease is defined as disease that has recurred >=6 months after completion of therapy. Refractory disease is defined as disease that either progressed during therapy or progressed within 6 months (<6 months) of completion of therapy;
-Failed previous HDT-ASCT or not eligible for HDT-ASCT at screening. If ineligible for HDT-ASCT, the decision must have been based on age, performance status, comorbidity, and/or insufficient response to prior treatment;
-Has measurable disease:
* A fluorodeoxyglucose-positron emission tomography (FDG-PET) scan demonstrating positive lesion(s) compatible with computed tomography (CT)- or magnetic resonance imaging (MRI)-defined anatomical tumor sites;
* >=1 measurable nodal lesion (long axis >1.5 cm and short axis >1.0 cm) and/or >=1 measurable extranodal lesion (long axis >1.0 cm) on CT scan or MRI;
-Absolute neutrophil count >=1.0 x 109/L (growth factor permitted);
-Platelet count >75 x 109/L (or >50 x 109/L if bone marrow involvement or splenomegaly);
-Alanine aminotransferase and aspartate aminotransferase level <=3 times the upper limit of normal (x ULN);
-Total bilirubin level <=2 x ULN, unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin;
-Estimated glomerular filtration rate (eGFR) >=50 mL/min/1.73 m2;
-Prothrombin time (PT)/international normalized ratio (INR)/activated partial thromboplastin time (aPTT) <=1.5 x ULN, unless receiving anticoagulation;
-Life expectancy >2 months on SOC treatment.

Exclude criteria

- Primary central nervous system (CNS) tumor or known CNS involvement as assessed by brain MRI at screening or by CT and lumbar puncture (if MRI contraindicated);
- Any prior therapy with a bispecific antibody targeting CD3 and CD20
- History of severe allergic or anaphylactic reactions to anti-CD20 antibody therapy;
- Contraindication to any component of SOC regimen selected prior to randomization;
- Major surgery within 4 weeks prior to randomization;
- Chemotherapy and other non-investigational antineoplastic agents (except CD20 mAbs) within 4 weeks or 5 half-lives (whichever is shorter) prior to randomization;
- Any investigational drug within 4 weeks or 5 half-lives, whichever is longer, prior to randomization;
- ASCT within 100 days of randomization;
- Treatment with CAR-T therapy within 100 days prior to randomization;
- Receiving immunosuppressive therapy, including more than the equivalent of 20 mg of prednisolone daily, unless for disease control;
- Seizure disorder requiring anti-epileptic therapy;
- Vaccination with live vaccines within 28 days prior to randomization;
- Clinically significant cardiovascular disease, including:
* Myocardial infarction within 1 year prior to randomization, or unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure, New York Heart Association Class III-IV) cardiac arrhythmia (CTCAE Version 5.0 Grade 2 or higher), or clinically significant electrocardiogram (ECG) abnormalities;
* Stroke within 6 months prior to randomization;
- Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) >470 msec;
- Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results;
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection requiring systemic treatment at time of randomization;
- Known history of seropositivity for human immunodeficiency virus (HIV) infection;
- Active hepatitis B virus (HBV) (DNA polymerase chain reaction [PCR]-positive) or hepatitis C (RNA PCR-positive infection). Subjects with evidence of prior HBV but who are PCR-negative are permitted in the trial but should receive prophylactic antiviral therapy. Subjects who received treatment for hepatitis C that was intended to eradicate the virus may participate if hepatitis C RNA levels are undetectable.
- Has known past or current malignancy other than inclusion diagnosis, except for:
* Cervical carcinoma of Stage 1B or less;
* Non-invasive basal cell or squamous cell skin carcinoma;
* Non-invasive, superficial bladder cancer;
* Prostate cancer with a current prostate specific antigen (PSA) level <0.1 ng/mL;
* Any curable cancer with a complete response of >2 years duration;
- Has known or suspected allergies, hypersensitivity, or intolerance to epcoritamab or its excipients (refer to the Investigator's Brochure for more information);
- Contraindication to all uric acid lowering agents;
- A woman of childbearing potential with a positive serum or urine pregnancy test at screening. Female subjects must also agree not to breastfeed during the entire trial and until 12 months after the last administration of study drug;
- Clinically significant liver disease, including active hepatitis, current alcohol abuse, or cirrhosis;
- Suspected active or latent tuberculosis as documented by interferon gamma release assay;
- Receiving immunostimulatory agent;
- Prior allogeneic hematopoietic stem cell transplantation

Related Information

• Primary Sponsor: Vindelov Signe Diness
• Secondary Sponsor: AbbVie