Trial Title:
Epcoritamab, Zanubrutinib, and Rituximab (EZR) for R/R FL Relapsed or Refractory Follicular Lymphoma
NCT ID:
NCT06563596
Condition:
Follicular Lymphoma
Lymphoma
Non-Hodgkin Lymphoma
Relapsed Lymphoma
Refractory Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Rituximab
Zanubrutinib
Conditions: Keywords:
Follicular Lymphoma
Lymphoma
Non-Hodgkin Lymphoma
Relapsed Lymphoma
Refractory Lymphoma
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Zanubrutinib
Description:
Bruton tyrosine kinase inhibitor, 80 mg immediate-release capsule, taken orally per
protocol.
Arm group label:
Rituxam + Zanubrutinib + Epcoritamab
Other name:
BDB-3111
Other name:
Brukinsa
Intervention type:
Drug
Intervention name:
Rituximab
Description:
Chimeric anti-CD20 monoclonal antibody, 10 or 50 mL single-use vials, via intravenous
infusion per institutional standard.
Arm group label:
Rituxam + Zanubrutinib + Epcoritamab
Other name:
MabThera
Other name:
Riabni
Other name:
Ruxience
Other name:
Truxima
Other name:
ABP 798
Other name:
IDEC-C2B8
Intervention type:
Drug
Intervention name:
Epcoritamab
Description:
Bispecific antibody, 5 or 60 mg/mL vials, via subcutaneous (under the skin) injection per
protocol.
Arm group label:
Rituxam + Zanubrutinib + Epcoritamab
Other name:
GEN3013
Summary:
The purpose of this study is to determine how effective and safe the combination of
epcoritamab, zanubrutinib, and rituximab is in treating participants with relapse or
refractory Follicular Lymphoma (FL).
- The names of the study drugs involved in this research study are:
- Epcoritamab (a type of antibody)
- Zanubrutinib (a type of Bruton tyrosine kinase inhibitor)
- Rituximab (a type of monoclonal antibody)
Detailed description:
This is an open-label, multicenter, phase II study to evaluate the efficacy and safety of
epcoritamab, zanubrutinib, and rituximab (EZR) for participants with relapsed or
refractory follicular lymphoma (FL). The trial will commence with a six participant
lead-in cohort.
The U.S. Food and Drug Administration (FDA) has approved epcoritamab for people who have
received at least 2 prior treatments for follicular lymphoma.
The U.S. FDA has approved zanubrutinib (in combination with a drug called obinutuzumab)
for people who have received at least 2 prior treatments for follicular lymphoma.
The FDA has also approved rituximab as a treatment option for follicular lymphoma.
The research study procedures include screening for eligibility, in-clinic visits, urine
tests, blood tests, stool samples, saliva samples, electrocardiograms (ECGs), bone marrow
biopsies, Computerized Tomography (CT) scans, Positron Emission Tomography (PET) scans,
and questionnaires.
Participants will receive study treatment for approximately 24 months and will be
followed every 6 months thereafter for up to 10 years.
It is expected that about 24 people will take part in this research study.
Genmab is supporting this research study by providing the study drug, epcoritamab, and
funding for the study. BeiGene is supporting this research study by providing the study
drug, zanubrutinib, and funding for the study.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Histologically confirmed diagnosis of CD20+ FL (grade 1-3A) (at time of trial entry)
with review of the diagnostic pathology specimen at one of the participating
institutions. Patients with current histologic transformation are excluded.
- Receipt of at least one prior line of therapy for FL (with prior treatment including
both a CD20 monoclonal antibody and an alkylating agent).
- Measurable disease, defined as ≥1 measurable nodal lesion (long axis >1.5 cm or
short axis >1.0 cm) or ≥1 measurable extra-nodal lesion (long axis >1.0 cm) on PET,
CT, or magnetic resonance imaging (MRI). Disease should be FDG-avid based on PET.
- Meets at least one criterion to begin treatment based on the modified GELF (Groupe
d'Etude des Lymphomes Folliculaires) criteria:
- Symptomatic adenopathy
- Organ function impairment due to disease involvement, including cytopenias due
to marrow involvement (WBC <1.5x109/L; absolute neutrophil count [ANC]
<1.0x109/L, Hgb <10g/dL; or platelets <100x109/L)
- Constitutional symptoms (defined as persistent fevers >100.4 F, shaking chills,
drenching night sweats, or loss of >10% of body weight within a 6 month period)
- Any nodal or extranodal tumor mass >7 cm in maximum diameter
-->3 nodal sites of involvement >3 cm
- Local compressive symptoms or imminent risk thereof
- Splenomegaly (craniocaudal diameter > 16cm on CT imaging)
- Clinically significant pleural or peritoneal effusion
- Leukemic phase (>5x109/L circulating malignant cells)
- Rapid generalized disease progression
- Renal infiltration
- Bone lesions
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. (Appendix A)
- Age ≥18 years.
- Adequate hematologic and organ function:
- Absolute neutrophil count > 1.0x109/L unless due to marrow involvement by
lymphoma in which case ANC must be >0.5x109/L
- Platelets > 75 x109/L, unless due to marrow involvement by lymphoma, in which
case platelets must be >50 x109/L
- Estimated CrCl (based on Cockcroft Gault or MDRD) ≥ 45ml/min or
≥45ml/min/1.73m2
- Total bilirubin < 1.5 X ULN, unless Gilbert syndrome, in which case direct
bilirubin must be < 1.5 x ULN
- AST/ALT < 2.5 X ULN, unless documented liver involvement by lymphoma, in which
case AST/ALT must be <5 x ULN
- Ability to understand and the willingness to sign a written informed consent
document.
- Willingness to provide a pre-treatment tumor sample by core needle or excisional
surgical biopsy. A fresh biopsy is strongly encouraged, but an archival sample is
acceptable if it is collected within 90 days and without intervening treatment and
the following provisions are met: 1) availability of a tumor-containing
formalin-fixed, paraffin-embedded (FFPE) tissue block, 2) if the tumor containing
FFPE tissue block cannot be provided in total, sections from this block should be
provided that are freshly cut and mounted on positively-charged glass slides.
Preferably, 25 slides should be provided; if not possible, a minimum of 15 slides is
required. Exceptions to this criterion may be made with approval of the
Sponsor-Investigator.
- Willingness to remain abstinent1 or to use two effective contraceptive methods that
result in a failure rate of <1% per year from screening until: (a) at least 3 months
after pre- treatment with rituximab, 12 months after the last dose of epcoritamab,
or 3 months after the last dose of zanubrutinib, whichever is longer, if the patient
is a male or (b) until at least 18 months after pre-treatment with rituximab, 12
months after the last dose of epcoritamab, or 3 months after the last dose of
zanubrutinib, whichever is longer, if patient is a female. Examples of contraceptive
methods with a failure rate of <1% per year include:
- Tubal ligation, male sterilization, hormonal implants, established proper use
of hormonal contraceptives that inhibit ovulation, hormone-releasing
intrauterine devices, and copper intrauterine devices.
- Alternatively, two methods (e.g., two barrier methods such as a condom and a
cervical cap) may be combined to achieve a failure rate of <1% per year.
Barrier methods must always be supplemented with the use of a spermicide.
- True abstinence is acceptable when this is in line with the preferred and usual
lifestyle of the subject. In contrast, periodic abstinence (eg, calendar,
ovulation, symptothermal, post-ovulation methods) and withdrawal are not
acceptable methods of contraception.
Exclusion Criteria:
- Patients who require systemic immunosuppressive therapy for an ongoing medical
condition will be excluded. For corticosteroids, patients receiving a prednisone
dose of >10 mg daily (or equivalent) will not be eligible. A short course of
steroids (up to 14 days) for lymphoma-related symptom palliation or for prophylaxis
(i.e., IV contrast allergy) is allowed, in which case patients should be off
steroids prior to treatment start.
- Patients with bulky cervical adenopathy that is compressing the upper airway or
could result in significant airway compression during a tumor flare event.
- Patients, who have had a major surgery or significant traumatic injury within 4
weeks of start of study drug, patients who have not recovered from the side effects
of any major surgery (defined as requiring general anesthesia).
- Presence of HCV antibody. Patients with presence of HCV antibody are eligible if HCV
RNA is undetectable (NOTE: the limit of detection for HCV RNA must have a
sensitivity of < 15 IU/mL). Subjects who received treatment for HCV that was
intended to eradicate the virus and who have an undetectable HCV RNA may participate
without serial HCV RNA screening. Other patients may participate if they are willing
to undergo every 3- month monitoring for HCV reactivation.
- Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody
(HBcAb). Patients with positive hepatitis B serologies with undetectable HBV DNA
(NOTE: the limit of detection for HBV DNA must have a sensitivity of < 20 IU/mL) are
permitted in the trial but should receive prophylactic antiviral therapy (i.e.
entecavir) and undergo every 3 month HBV DNA monitoring.
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
(excluding fungal infections of nail beds) requiring antimicrobial therapy at trial
enrolment or significant infections within 2 weeks prior to the first dose of
epcoritamab.
- Subject has a known active severe acute respiratory syndrome coronavirus 2 (SARS-
CoV-2) infection. If a subject has signs/symptoms suggestive of SARS-CoV-2 infection
or has had recent known exposure to someone with SARS-CoV-2 infection, the subject
must have a negative molecular (e.g., PCR) test, or 2 negative antigen test results
at least 24 hours apart, to rule out SARS-CoV-2 infection. Subjects who do not meet
SARS- CoV-2 infection eligibility criteria must be screen failed and may only
rescreen after they meet the following SARS-CoV-2 infection viral clearance
criteria:
- No signs/symptoms suggestive of active SARS-CoV-2 infection
- Negative molecular (e.g., PCR) result or 2 negative antigen test results at
least 24 hours apart
- Prior history of another malignancy (except for non-melanoma skin cancer, in situ
cervical or breast cancer, or Gleason 6 prostate cancer managed with observation)
unless disease free for at least 2 years.
- Patients should not have received immunization with attenuated live vaccine within
one week of study entry or during study period. Vaccination with live vaccines
within 28 days of the first dose of study treatment is prohibited.
- Patients who have any severe and/or uncontrolled medical conditions or other
conditions that could affect their participation in the study or limit adherence to
study requirements.
- Patients with any one of the following currently on or in the previous 6 months will
be excluded: myocardial infarction, congenital long QT syndrome, torsade de pointes,
unstable angina, coronary/peripheral artery bypass graft, cardiac arrhythmia (CTCAE
grade 3 or higher), or cerebrovascular accident. History of Mobitz II second-degree
or third-degree heart block without a permanent pacemaker in place. Uncontrolled
hypertension as indicated by ≥ 2 consecutive blood pressure measurements showing
systolic blood pressure > 170 mm Hg and diastolic blood pressure > 105 mm Hg at
screening.
- Patients with 1) New York Heart Association Class III or IV heart failure or known
ejection fraction of <45%, 2) MI within 6 months prior to screening, 3) unstable
angina within 3 months before screening, or 4) history of clinically significant
arrhythmias within 6 months of screening (eg sustained Vtach, Vfib, torsades de
pointes).
- Inability to comply with protocol mandated restrictions.
- Patients who are pregnant, breast-feeding, or intending to become pregnant during
the study.
- Prior solid organ or allogeneic stem cell transplantation.
- History of known or suspected hemophagocytic lymphohistiocytosis (HLH).
- History of clinically significant autoimmune disease, including but not limited to
myocarditis, pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis,
systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease,
vascular thrombosis associated with antiphospholipid syndrome, Wegener's
granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis,
vasculitis, or glomerulonephritis.
- Patients with a remote history of, or well controlled, autoimmune disease who meet
above criteria may be eligible to enroll after consultation with the
Sponsor-Investigator.
- Inability to tolerate anti-CD20 mAb therapy or known allergy or intolerance to any
component or excipient of epcoritamab.
- Known central nervous system involvement
- Neuropathy > grade 1(based on CTCAE grading)
- Treatment with CAR-T therapy within 100 days prior to first dose of epcoritamab.
- Treatment with an investigational drug within 4 weeks prior to the first dose of
study treatment.
- Chemotherapy and other non-investigational anti-neoplastic agents (except CD20 mAbs)
within 4 weeks prior to the first dose of study treatment.
- Participants who require warfarin or other vitamin K antagonists for
anticoagulation. Other anticoagulants including direct oral anticoagulants (i.e.
apixaban, rivaroxaban) and low-molecular weight heparin are allowed.
- Participants who are known at the time of study entry to require concomitant
treatment with any medications or substances that are strong CYP3A inducers. Because
the lists of these agents are constantly changing, it is important to regularly
consult a frequently updated medical reference. As part of the enrollment/informed
consent procedures, the participant will be counseled on the risk of interactions
with other agents, and what to do if new medications need to be prescribed or if the
participant is considering a new over- the-counter medicine or herbal product.
- Unable to swallow capsules or disease significantly affecting gastrointestinal
function, such as malabsorption syndrome.
- History of severe bleeding disorder such as hemophilia A, hemophilia B, von
Willebrand disease, or history of spontaneous bleeding requiring blood transfusions
or other medical interventions. Requires ongoing treatment with warfarin or warfarin
derivatives.
- Prior exposure to a BTK inhibitor
- Screening 12-lead ECG showing a baseline QTcF (Fridericia's correction) > 480 msec.
- History of stroke or intracranial hemorrhage within 6 months before first dose of
study drug.
- Major surgery ≤ 4 weeks before the first dose of study treatment or planned during
study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Brigham and Women's Hospital
Address:
City:
Boston
Zip:
02215
Country:
United States
Contact:
Last name:
Reid Merryman, MD
Phone:
617-632-6844
Email:
Reid_merryman@dfci.harvard.edu
Investigator:
Last name:
Reid Merryman, MD
Email:
Principal Investigator
Facility:
Name:
Dana-Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Contact:
Last name:
Reid Merryman, MD
Phone:
617-632-6844
Email:
Reid_merryman@dfci.harvard.edu
Investigator:
Last name:
Reid Merryman, MD
Email:
Principal Investigator
Start date:
February 2025
Completion date:
March 1, 2029
Lead sponsor:
Agency:
Reid Merryman, MD
Agency class:
Other
Collaborator:
Agency:
BeiGene
Agency class:
Industry
Collaborator:
Agency:
Genmab
Agency class:
Industry
Source:
Dana-Farber Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06563596
