A Phase 3 Trial of Epcoritamab vs Investigator’s Choice Chemotherapy in R/R DLBC
- Conditions
- Therapeutic area: Diseases [C] - Cancer [C04]B-cell LymphomaMedDRA version: 20.0Level: HLTClassification code 10012819Term: Diffuse large B-cell lymphomasSystem Organ Class: 100000004851
- Registration Number
- EUCTR2020-003016-27-AT
- Lead Sponsor
- Genmab A/S
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 480
1. Must be at least 18 years of age;
2. ECOG PS score of 0-2;
3. 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 with MYC and BCL2 and / or BCL6
traslocations
c. FL Grade 3B
d. T-cell/histiocyte-rich large B-cell lymphoma
4. CD20-positivity at representative tumor biopsy based on the
pathology report;
5. 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);
6. 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;
7. 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;
8. Absolute neutrophil count =1.0 x 10e9/L (growth factor permitted);
9. Platelet count >75 x 10e9/L (or >50 x 10e9/L if bone marrow
involvement or splenomegaly);
10. Alanine aminotransferase and aspartate aminotransferase 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 ALAT and ASAT levels are = 5 xULN;
11. 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 =5 ULN;
12. Estimated glomerular filtration rate (eGFR) =50 mL/min/1.73m2 as calculated by Cockcroft-Gault;
13. PT/INR/aPTT = 1.5 xULN, unless receiving anticoagulation;
14. 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;
15. 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 Cycle
1;
16. 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 must agree not to donate sperm during the
trial and for 12 months after receiving the last administration of trial
treatment.
17. Life expectancy > 2 months on SOC treatment.
18. Able to provide baseline fresh or archival tumor biopsies.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 192
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 288
1. 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);
2. Any prior therapy with a bispecific antibody targeting CD3 and CD20;
3. History of severe allergic or anaphylactic reactions to anti-CD20
antibody therapy;
4. Contraindication to any component of SOC regimen selected prior to
randomization;
5. Major surgery within 4 weeks prior to randomization;
6. Chemotherapy and other non-investigational antineoplastic agents
(except CD20 mAbs) within 4 weeks or 5 half-lives (whichever is
shorter) prior to randomization;
7. ASCT within 100 days of randomization;
8. Treatment with CAR-T therapy within 100 days prior to randomization;
9. Receiving immunosuppresive therapy, including more than the
equivalent of =20 mg of prednisolone daily, unless for disease control;
10. Seizure disorder requiring anti-epileptic therapy;
11. 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-CoV-
2) vaccinations are not allowed;
12. Clinically significant cardiovascular disease
13. Screening 12-lead ECG showing a baseline QT interval as corrected
by Fridericia's formula (QTcF) >470 msec;
14. Evidence of significant, uncontrolled concomitant diseases that could
affect compliance with the protocol or interpretation of results;
15. Known active bacterial, viral, fungal, mycobacterial, parasitic, or
other infection requiring systemic treatment at time of randomization;
16. Known history of positivity for human immunodeficiency virus (HIV)
infection; Note: HIV testing is required at screening only if required per local health authorities or institutional standards.
17. 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.
18. 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;
19. Contraindication to all uric acid lowering agents;
20. 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;
21. Clinically significant liver disease, including active hepatitis, current
alcohol abuse, or cirrhosis;
22. Active tuberculosis or history of completed treatment for active tuberculosis within the past 12 months.
23. Receiving immunostimulatory agent;
24. Pr
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Compare the clinical efficacy of epcoritamab to standard of care (SOC) (R-GemOx or BR);Secondary Objective: Compare other measures of epcoritamab efficacy to SOC;Primary end point(s): - Overall survival (OS);Timepoint(s) of evaluation of this end point: Please refer to protocol
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Progression-free survival (PFS) determined by Lugano criteria per independent review committee (IRC) assessment and investigator assessment<br>- Overall response rate (ORR) determined by Lugano criteria per IRC assessment and investigator assessment<br>- Complete response (CR) rate, determined by Lugano criteria per IRC assessment and investigator assessment<br>- Duration of response (DOR) determined by Lugano criteria per IRC assessment and investigator assessment;Timepoint(s) of evaluation of this end point: Please refer to protocol