This study has been transitioned to CTIS with ID 2023-504830-23-00 check the CTIS register for the current data. Compare the clinical efficacy of Epcoritamab to SOC (R-GemOx or BR)
ID
Source
Brief title
Condition
- Lymphomas non-Hodgkin's B-cell
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Overall survival
Secondary outcome
- Progression-free survival (PFS) determined by Lugano criteria per independent
review committee (IRC) assessment and investigator assessment
- Overall response rate (ORR) determined by Lugano criteria per IRC assessment
and investigator assessment
- Complete response (CR) rate, determined by Lugano criteria per IRC assessment
and investigator assessment
- Duration of response (DOR) determined by Lugano criteria per IRC assessment
and investigator assessment
Background summary
30-40% of the patients diagnosed with diffuse large B-cell lymphoma (DLBCL)
will have R/R (relapse/refractory) disease. DLBCL is the most common type of
non- Hodgkin lymphoma (NHL). The cure rate for R/R patients is less than 10%.
Current therapies for R/R patients are limited, hence there is a need for novel
therapies.
Epcoritamab is a fully human IgG1-bispecific antibody targeting CD3+ T-cells
and CD20+ B cells; the mechanism of action is engagement of T cells as effector
cells to induce killing of CD20- expressing B cells and tumor cells. CD20 is a
clinically validated target for treatment of B-cell malignancies. This
mechanism of action is different compared to chemotherapy or a conventional
CD20- targeting mAb.
Subjects with R/R DLBCL may benefit from treatment with Epcoritamab in terms of
disease reduction or control.
Study objective
This study has been transitioned to CTIS with ID 2023-504830-23-00 check the CTIS register for the current data.
Compare the clinical efficacy of Epcoritamab to SOC (R-GemOx or BR)
Study design
A randomized, open-label, phase 3 study
Intervention
Eligible subjects will be randomized to either epcoritamab or investigators
choice chemotherapy (i.e., sites will a priori choose either R-GemOx or BR)
(SOC).
Epcoritamab arm:
Epcoritamab will be administered as a SC injection in 28- day cycles as
follows:
• Cycle 1: 0.16 mg SC on Day 1 (priming dose), 0.8 mg SC on Day 8 (intermediate
dose), 48 mg (full dose) SC on Days 15 and 22 (once weekly)
• Cycles 2 and 3: 48 mg SC on Days 1, 8, 15, 22 (once weekly)
• Cycles 4 through 9: 48 mg SC on Days 1 and 15 (every 2 weeks)
• Cycle 10 onward: 48 mg SC on Day 1 (every 4 weeks)
Investigators choice chemotherapy arm:
Subjects will receive 1 of the 2 chemotherapy options below:
- Bendamustine and rituximab (BR): rituximab 375 mg/m2 IV on Day 1 and
bendamustine 90 mg/m2 IV on Days 1 and 2 of each 21-day cycle for up to 6
cycles.
- Rituximab, gemcitabine and oxaliplatin (R-GemOx): rituximab 375 mg/m2 IV on
Days 1 and 15 and gemcitabine 1000 mg/m2 IV followed by oxaliplatin 100 mg/m2
IV on Days 2 and 16 of each 28-day cycle for up to 4 cycles.
Study burden and risks
Treatment with epcoritamab involves subcutaneous injection (the first 4 visits
followed by hospitalization and premedication). Risks associated with
participation are side effects, among which tumor lysis syndrome, cytokine
release syndrome and neurological
symptoms (ICANS).
The risk to subjects in this trial should be minimized by compliance with the
eligibility criteria, trial procedures, close monitoring, and proper/prompt
management of TEAEs.
The patients will need to follow appointments for visits and will undergo
physical examination, ECOG, neurological evaluation (ICANS), ECG,
venapunctions, scans and biopsies. Patients will be interviewed on past and
present medical conditions, diseases,
surgeries, allergies and previous medicines. Also, patients should not become
pregnant, breastfeed a baby, father a child or donate sperm or eggs while
participating in this trial and must agree to use a highly effective method of
birth control from the time of screening until 12 months after the last dose of
epcoritamab. Patients will be tested for hepatitis B, C and cytomegalovirus,
HIV.
Subjects with R/R DLBCL may benefit from treatment with epcoritamab in terms of
disease reduction or control, as epcoritamab has a different mode of action
from chemotherapy and direct CD20-targeting monoclonal antibodies. It is
expected that toxicities can be managed with standard supportive care. The
potential benefit of therapy with epcoritamab is expected to outweigh the
treatment-related risks. Treatment with investigator*s choice
immunochemotherapy regimens is according to local guidelines and represents
standard of care treatment with established benefit-risk profiles.
With safety precautions and a close monitoring plan in place, the described
risks are outweighed by the potential benefit subjects might receive from
epcoritamab.
More detailed information about the known and expected benefits and risks and
reasonably expected AEs of epcoritamab are found in the IB
Kalvebod Brygge 43
Copenhagen V DK-1560
DK
Kalvebod Brygge 43
Copenhagen V DK-1560
DK
Listed location countries
Age
Inclusion criteria
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.
Exclusion criteria
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 immunostimulatory agent;
24. Prior allogeneic hematopoietic stem cell transplantation.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-504830-23-00 |
| EudraCT | EUCTR2020-003016-27-NL |
| CCMO | NL75079.056.20 |