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About
phase II, response-adaptive, open-label, multicenter study aiming to include 80 patients in 78 months. Patients will receive 3 cycles of epcoritamab monotherapy and, since cycle 4, they can continue with epcoritamab monotherapy until cycle 12 or change to combination therapy (epcoritamab + tafasitamab + lenalidomide) until cycle 15. Patients will be followed up to 5 years.
Full description
Epcoritamab is a full-length bispecific IgG1 antibody directed against two proteins, CD3 on the T lymphocyte and CD20 on the lymphoma cell. This antibody redirects and activates T cells, generating an immune synapse that eventually eliminates malignant cells expressing CD20.
Previous studies have demonstrated that Epcoritamab has potent antitumor activity as a monotherapy agent, with a favorable and manageable safety profile.
Since its efficacy is so favorable it is reasonable to think that it could be an excellent option for first-relapse patients. However, to date, there is no data on this therapy's usefulness as second-line treatment. Therefore we intend to evaluate the efficacy of Epcoritamab as a treatment option for patients with first-relapse LBCL.
The purpose of this study is to determine the efficacy of Epcoritamab as second line treatment for LBCL patients. On the basis of the clinical experience, it is hypothesized that Epcoritamab would provide a better complete response rate (CRR) in comparison to Platinum-based immunochemotherapy (CRR=25%), Polatuzumab-Bendamustin Rituximab (CRR=40%) and Tafasitamab-Lenalidomide (CRR=43%).
Enrollment
Sex
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Inclusion criteria
Written informed consent must be obtained before any study-specific assessment is performed.
Age >18 years
Patients with Relapse/Refractory histologically confirmed LBCL, including, Diffuse Large B Cell Lymphoma (DLBCL); Primary Mediastinal Large B Cell Lymphoma (PMBCL), High-grade B-cell lymphoma (HGBCL); and grade 3B Follicular Lymphoma.
Relapsed disease is defined as complete remission to first line therapy followed by a recurrence of the disease after a minimum of 6 months of completion of first-line therapy. A biopsy at the time of relapse is recommended but not mandatory.
Refractory disease is defined as no objective response to first line therapy (biopsy not mandatory if diagnostic sample available). Four groups of patients are eligible:
Patients must have received adequate first-line therapy including at a minimum: an anti-CD20 monoclonal antibody (rituximab or obinutuzumab), and CHOP (cyclophosphamide, hydroxydaunomycin, oncovin, and prednisone) or CHOP-like chemotherapy.
At the investigator's discretion, the patient should not be a candidate for 1st relapse CAR-T therapy or unwilling to receive CAR-T therapy.
Patients must be autologous stem cell transplantation (ASCT)-ineligible: Age ≥65 and/or HTC-CI ≥3 or or unwilling to receive transplant.
PET positive disease.
Performance status according to Eastern Cooperative Oncology Group (ECOG) 0 to 2.
Patients meeting with the following hematology values:
Female patients of child-bearing potential must have a negative urine or serum pregnancy test at screening and agree to use highly effective methods of contraception (e.g., established use of oral, injected or implanted combined (estradiol and progesterone containing) hormonal contraception; placement of an intrauterine device (IUD) or intrauterine system (IUS) upon enrollment according to the recommendations provided by Clinical Trial Facilitation Group (CTFG), during the treatment period and for 4 months after the last dose of study medication. Moreover, the patient must agree to ongoing pregnancy testing during the course of the study, and after study therapy has ended. This applies even if the patient practices complete and continued sexual abstinence.
Women not of childbearing potential are defined as: premenarchal; postmenopausal (greater than 50 years of age with amenorrhea for at least 12 months or any age with amenorrhea for at least 6 months and a serum follicle stimulating hormone (FSH) level greater than 40 IU per L or milli-International unit (mIU) per mL); permanently sterilized (e.g., bilateral tubal occlusion [which includes tubal ligation procedures as consistent with local regulations], hysterectomy, bilateral salpingectomy, bilateral oophorectomy); or otherwise be incapable of pregnancy.
Male patients must use a reliable method of contraception (if sexually active with a female of child-bearing potential) upon enrollment according to the recommendations provided by CTFG, during the treatment period, and for 4 months following the last dose of investigational drug or agreement to remain abstinent. Agreement to refrain from donating blood or sperm during the study participation and for 4 months after the last dose of study medication.
Women must agree not to donate blood or oocytes during the course of the study and for 4 months after the last dose of study medication. Restrictions concerning blood donation apply as well to females who are not of childbearing potential. Men must also not donate sperm during the trial and for 4 months after receiving the last dose of study drug.
Females of childbearing potential must refrain from breastfeeding during the course of the study and for 4 months after the last dose of study medication.
Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
Not included in other clinical trial or treated with an experimental drug.
Exclusion criteria
Patients who received more than one prior line of systemic therapy
Patients with detectable Central Nervous System (CNS) lymphoma
Significant organ function impairment:
Serious accompanying disorder leading to impaired organ function causing significant clinical problems and reduced life expectancy of less than 3 months.
Have a history of deep venous thrombosis/embolism, threatening thromboembolism or known thrombophilia or are at a high risk for a thromboembolic event in the opinion of the investigator and who are not willing/able to take venous thromboembolic event prophylaxis during the entire treatment period
Known clinically significant cardiac disease, including:
Known past or current malignancy other than inclusion diagnosis, except for: Cervical carcinoma of Stage 1B or less; Non-invasive basal cell or squamous cell skin carcinoma; Non-invasive, superficial bladder cancer; Localized low grade prostate cancer (up to Gleason score 6); DCIS of the breast; Other malignancy that has been treated with curative intent and has remained in remission for 3 years.
Previous ASCT.
Prior anti-CD3 and CD20 bispecific antibodies therapy or prior treatment with tafasitamab.
Presence of severe infection that is uncontrolled or requiring IV antimicrobials for management.
History of HIV infection or acute or chronic active hepatitis B or C infection.
Females who are pregnant or breastfeeding.
Richter's transformation or prior chronic lymphocytic leukemia (CLL).
Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 4 weeks prior to Cycle 1 Day 1.
Recent major surgery (within 4 weeks before the start of Cycle 1 Day 1) other than for diagnosis.
Vaccination with a live vaccine or COVID-19 vaccination within 4 weeks prior to treatment.
History of hypersensitivity to any of the study drugs or their ingredients or to drugs with similar structure. History of severe allergic or anaphylactic reactions to human, humanized, chimeric, or murine monoclonal antibodies.
Close affiliation with the investigator (e.g. a close relative) or persons working at the study site.
Primary purpose
Allocation
Interventional model
Masking
80 participants in 2 patient groups
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Central trial contact
Ana María Méndez; Auxi Moreno
Data sourced from clinicaltrials.gov
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