A Randomized, Open-Label, Phase 3 Trial of Epcoritamab vs Investigator*s Choice Chemotherapy in Relapsed/Refractory Diffuse Large B-cell Lymphoma
- Conditions
- lymphomanon-hodgkin lymphoma10025320
- Registration Number
- NL-OMON54027
- Lead Sponsor
- Genmab
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 17
1. Must be at least 18 years of age (>=20 years of age in Japan);
2. ECOG PS score of 0-2;
3. One of the confirmed histologies below with 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 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);
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 level <=3 times the upper limit of normal (xULN),
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 xULN, 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;
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.
1. Primary 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 by site;
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 cardiac 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 or lactating females;
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 immun
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Overall survival</p><br>
- Secondary Outcome Measures
Name Time Method <p>- Progression-free survival (PFS) determined by Lugano criteria per independent<br /><br>review committee (IRC) assessment and investigator assessment<br /><br>- Overall response rate (ORR) determined by Lugano criteria per IRC assessment<br /><br>and investigator assessment<br /><br>- Complete response (CR) rate, determined by Lugano criteria per IRC assessment<br /><br>and investigator assessment<br /><br>- Duration of response (DOR) determined by Lugano criteria per IRC assessment<br /><br>and investigator assessment</p><br>