EPCORITAMAB for Diffuse large B-cell lymphoma | B-cell lymphoma | Follicular lymphoma (grade 3B)

Inclusion criteria

• {"criterion_text":"- Must be at least 18 years of age\n- Subject must sign an 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\n- ECOG PS score of 0-2\n- One of the confirmed histologies below wiht CD20 positivity: a. DLBCL, NOS (according to the WHO 2016 classification), and including de novo or histologically transformed from follicular lymphoma (FL). b. \"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 c. FL Grade 3B d. T-cell/histiocyte-rich large B-cell lymphoma\n- CD20-positivity at representative tumor biopsy based on the pathology report;\n- Relapsed or refractory disease and previously treated with at least 1 line of systemic antineoplastic therapy including anti-CD20 mAbcontaining combination chemotherapy since lymphoma diagnosis (ie,having received R-CHOP or an equivalent regimen that would be considered adequate first-line treatment for DLBCL);\n- 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;\n- Has measurable disease: a. A fluorodeoxyglucose-positron emission tomography (FDG- PET) scan demonstrating positive lesion(s) compatible with computed tomography (CT) or magnetic resoncance imagining (MRI)-defined anatomical tumor sites b. ≥1 measurable nodal lesion (long axis >1.5 cm and short axis >1.0 cm) and/or ≥1 measurable extra-nodal lesion (long axis >1.0 cm) on CT scan or MRI;\n- Absolute neutrophil count ≥1.0 x 10e9/L (growth factor permitted)\n- Platelet count >75 x 10e9/L (or >50 x 10e9/L if bone marrow involvement or splenomegaly)\n- A female subject must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the entire trial, until 12 months after the last administration of trial treatment\n- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level ≤3 times the upper limit of normal (x ULN), unless enzyme elevation is due to a nonhepatic origin or lymphoma involvement of the liver and ALT and AST levels are ≤5 xULN\n- Total bilirubin level ≤2 x ULN, unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin or lymphoma involvement of the liver and total bilirubin is ≤5xULN\n- Estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m2 as calculated by Cockcroft-Gault\n- PT/INR/aPTT ≤1.5 xULN, unless receiving anticoagulation\n- A female subject with reproductive potential must agree to use adequate contraception during the trial, and for 12 months after the last administration of trial treatment. Adequate contraception is defined as highly effective methods of contraception\n- A female subject of childbearing potential must have a negative serum (beta-hCG) pregnancy test at screening and a negative serum or urine pregnancy test before treatment administration on Day 1 of every cycle\n- A male subject who is sexually active with a female of reproductive potential and has not had a vasectomy must agree to use a barrier method of birth control and (ie, condom) must agree not to donate sperm during the trial and for 12 months after receiving the last administration of trial treatment.\n- Life expectancy >2 months on SOC treatment."}

Exclusion criteria

• {"criterion_text":"- 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)\n- Has known past or current malignancy other than inclusion diagnosis, except for: a. Cervical carcinoma of Stage 1B or less b. Non-invasive basal cell or squamous cell skin carcinoma c. Non-invasive, superficial bladder cancer d. Prostate cancer with a current PSA level <0.1 ng/mL e. Any curable cancer with a complete response of >2 years duration\n- Contraindication to all uric acid lowering agents\n- Any prior therapy with a bispecific antibody targeting CD3 and CD20\n- 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\n- Clinically significant liver disease, including active hepatitis, current alcohol abuse, or cirrhosis\n- Active tuberculosis or history of completed treatment for active tuberculosis within the past 12 months\n- Receiving immunostimulatory agent\n- Prior allogeneic hematopoietic stem cell transplantation\n- History of severe allergic or anaphylactic reactions to anti-CD20 antibody therapy\n- Contraindication to any component of SOC regimen selected prior to randomization\n- Seizure disorder requiring anti-epileptic therapy\n- Major surgery within 4 weeks prior to randomization\n- Chemotherapy and other non-investigational antineoplastic agents (except CD20 mAbs) within 4 weeks or 5 half-lives (whichever is shorter) prior to randomization\n- ASCT within 100 days of randomization\n- Treatment with CAR-T therapy within 100 days prior to randomization\n- Receiving immunosuppressive therapy, including more than the equivalent of ≥20 mg of prednisolone daily, unless for control of lymphoma or intermittent prophylaxis/treatment of allergic reactions\n- Any investigational drug within 4 weeks or 5 half-lives, whichever is longer, prior to randomization\n- Has known or suspected allergies, hypersensitivity, or intolerance to epcoritamab or its excipients\n- Vaccination with live vaccines within 28 days prior to randomization. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever,rabies, Bacillus Calmette–Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. Experimental and/or non authorized severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccinations are not allowed\n- Clinically significant cardiovascular disease\n- Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) >470 msec\n- Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results\n- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection requiring systemic treatment at time of randomization\n- Known history of seropositivity for human immunodeficiency virus (HIV) infection. Note: HIV testing is required at screening only if required per local health authorities or institutional standards\n- 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"}

Primary endpoints

• {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Progression-free survival (PFS) determined by Lugano criteria per independent review committee (IRC) assessment","definition_or_measurement_approach":"Determined by Lugano criteria per independent review committee (IRC) assessment"}

Secondary endpoints

• {"endpoint_text":"- Progression-free survival (PFS) determined by Lugano criteria per investigator assessment","definition_or_measurement_approach":"Determined by Lugano criteria per investigator assessment"}
• {"endpoint_text":"- Overall response rate (ORR) determined by Lugano criteria per IRC assessment and investigator assessment","definition_or_measurement_approach":"Determined by Lugano criteria per IRC assessment and investigator assessment"}
• {"endpoint_text":"- Complete response (CR) rate determined by Lugano criteria per IRC assessment and investigator assessment","definition_or_measurement_approach":"Determined by Lugano criteria per IRC assessment and investigator assessment"}
• {"endpoint_text":"- Duration of response (DOR) determined by Lugano criteria per IRC assessment and investigator assessment","definition_or_measurement_approach":"Determined by Lugano criteria per IRC assessment and investigator assessment"}
• {"endpoint_text":"- Time to response (TTR) determined by Lugano criteria per IRC assessment and investigator","definition_or_measurement_approach":"Determined by Lugano criteria per IRC assessment and investigator assessment"}
• {"endpoint_text":"- Rate and duration of minimal residual disease (MRD) negative status","definition_or_measurement_approach":""}
• {"endpoint_text":"- PFS determined by Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) per IRC assessment","definition_or_measurement_approach":"Determined by LYRIC per IRC assessment"}
• {"endpoint_text":"- ORR determined by LYRIC per IRC assessment","definition_or_measurement_approach":"Determined by LYRIC per IRC assessment"}
• {"endpoint_text":"- CR rate determined by LYRIC per IRC assessment","definition_or_measurement_approach":"Determined by LYRIC per IRC assessment"}
• {"endpoint_text":"- DOR determined by LYRIC per IRC assessment","definition_or_measurement_approach":"Determined by LYRIC per IRC assessment"}
• {"endpoint_text":"- TTR determined by LYRIC per IRC assessment","definition_or_measurement_approach":"Determined by LYRIC per IRC assessment"}
• {"endpoint_text":"- Time to next anti-lymphoma therapy (TTNT)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Incidence and severity of adverse events (AEs)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Incidence and severity of changes in laboratory values","definition_or_measurement_approach":""}
• {"endpoint_text":"- Incidence of dose interruptions and delays","definition_or_measurement_approach":""}
• {"endpoint_text":"- Anti-epcoritamab antibody response","definition_or_measurement_approach":""}
• {"endpoint_text":"- Changes in lymphoma symptoms as measured by the Functional Assessment of Cancer Therapy – Lymphoma (FACT-Lym)","definition_or_measurement_approach":"Measured using the FACT-Lym patient-reported instrument"}

Primary sponsor

Full Name

Genmab A/S

Organisation Type

Pharmaceutical company

Country Of Registered Address

Denmark

Contract research organisations

Name

Eresearchtechnology Inc.

Responsibilities

Central ECG and ePRO

Name

Icon Clinical Research Limited

Responsibilities

Centralization of local laboratories

Name

IQVIA Limited

Responsibilities

Clinical operations and multiple trial support functions (various codes)

Name

Clinipace Inc.

Name

Fortrea Inc.

Third parties

• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Central ECG and ePRO","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Centralization of local laboratories","organisation_type":"Pharmaceutical company"}
• {"country":"China","full_name":"Macrostat (Shanghai) Clinical Research Co. Ltd.","duties_or_roles":"Biostatistics and programming","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"ICON Bioanalytical Laboratories","duties_or_roles":"PK & ADA Samples","organisation_type":"Health care"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"CellCarta","duties_or_roles":"FFPE for IHC and FISH","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Multiple functions (codes 1,11,12,2,5,7,8) including clinical trial information and operational support","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Adaptive Biotechnologies Corp.","duties_or_roles":"MRD and TCR sequencing","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Clinipace Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Pixilib","duties_or_roles":"Total metabolic tumour volume analyses (TMTV)","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"SGS Belgium","duties_or_roles":"iDMC unbliding vendor","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Fortrea Development Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Belgium","full_name":"SGS Belgium","duties_or_roles":"","organisation_type":"Pharmaceutical company"}