A Phase 3 Trial of Epcoritamab vs Investigator’s Choice Chemotherapy in R/R DLBC
- Conditions
- B-cell LymphomaMedDRA version: 20.0Level: HLTClassification code 10012819Term: Diffuse large B-cell lymphomasSystem Organ Class: 100000004851Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-003016-27-FR
- 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 (=20 years of age in Japan);
2. ECOG PS score of 0-2;
3. Histologically confirmed CD20+ DLBCL, NOS (according to the WHO 2016 classification) and including:
a. Subjects with de novo or histologically transformed (including Richter’s transformation).
b. Subjects with double-hit” or triple-hit”
c. Subjects with FL Grade 3B;
4. CD20-positivity at most recent (previous or current) 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;
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 FDG- PET scan demonstrating positive lesion compatible with CT or MRI-defined anatomical tumor sites
b. =1 measurable nodal lesion (long axis >1.5 cm and short axis >1.0 cm) 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);
11. Total bilirubin level =2 xULN, unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin;
12. Estimated GFR =40 mL/min/1.73m2;
13. 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;
14. 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;
15. 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.
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 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. Radiation therapy, or major surgery within 4 weeks prior to randomization;
6. Chemotherapy 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 30 days prior to randomization;
9. Cumulative dose of corticosteroids more than the equivalent of =140 mg of prednisone within 2-week period prior to randomization;
10. Seizure disorder requiring anti-epileptic therapy;
11. Vaccination with live vaccines within 28 days prior to the first dose of epcoritamab;
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 or positive test results confirming HIV infection;
17. Active HBV (DNA 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 HCV 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. Suspected active or latent tuberculosis;
23. Positive test results for the HTLV-1.
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