Response-adaptive to Epcoritamab In FIrst Relapse: A Phase II, response-adaptive, Open-Label, Multicenter Study to Evaluate the Efficacy of Eptoritamab in Patients with Relapse/Refractory Large B Cell Lymphoma

Phase 2

Not yet recruiting

Conditions: Relapse/Refractory Large B Cell Lymphoma

Registration Number: 2024-514440-86-00

Lead Sponsor: Fundacion Geltamo

Brief Summary: The primary objective of the study is to evaluate the efficacy of Epcoritamab monotherapy by central evaluation as second line treatment for LBCL patients

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised, recruitment pending

Sex: Not specified

Target Recruitment: 80

Inclusion Criteria

Written informed consent must be obtained before any study-specific assessment is performed.

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.

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

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

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: Hemoglobin ≥8 g/dl (transfusion support permitted but not within 7 days of screening lab collection); Absolute neutrophil count (ANC) ≥ 1 X 10E9/L (growth factor support allowed in case of bone marrow involvement); Absolute lymphocyte count ≥ 0.1 x 10E9/L; Platelet count ≥ 70 x 10E9/L (unless secondary to bone marrow involvement, OR ≥50 x 10E9/L if documented bone marrow involvement). Platelet transfusions permitted but not within 7 days of screening lab collection.

Exclusion Criteria

Patients who received more than one prior line of systemic therapy

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. Individuals with positive HIV serology may be included if negative viral load and CD4 >200/mm3. For being included, patients should have controlled disease and been on treatment for at least 1 year. Individuals with history of hepatitis infection with positive antibodies (anti-HB and anti-HV) might be included if negative viral load (negative hepatitis B PCR). Patients who are HBcAb positive must receive HBV prophylaxis while on treatment. Patients with positive HbsAg are excluded. Patients who are hepatitis B PCR positive will be excluded. Patients who are hepatitis C RNA positive will be excluded.

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

Patients with detectable Central Nervous System (CNS) lymphoma

Significant organ function impairment: creatinine clearance calculated by Cockcroft-Gault ≤ 45 ml/min; direct bilirubin level < 2 x ULN (except in patients with Gilbert’s syndrome); alanine transaminase (ALT) and aspartate aminotransferase (AST) >3 × ULN or >5 × ULN in cases of documented liver involvement; clinically relevant pleural effusion; left ventricular ejection fraction (LVEF) ≤ 45%

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: Onset of unstable angina pectoris within 6 months of signing the patient informed consent form; Acute myocardial infarction within 6 months of signing the patient informed consent form; Congestive heart failure (grade III or IV as classified by the New York Heart Association; Left ventricular ejection fraction ≤45%.

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.

Study & Design

Study Type: Not specified

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The efficacy of Epcoritamab monotherapy will be centrally evaluated by the best CRR at any moment since initiation. The CRR will be assessed by PET-CT according to Lugano Classification (Appendix 3) and is defined as the proportion of patients who achieve a best response of complete response (CR) at any moment since initiation of Epcoritamab first administration		The efficacy of Epcoritamab monotherapy will be centrally evaluated by the best CRR at any moment since initiation. The CRR will be assessed by PET-CT according to Lugano Classification (Appendix 3) and is defined as the proportion of patients who achieve a best response of complete response (CR) at any moment since initiation of Epcoritamab first administration

Secondary Outcome Measures

Name	Time	Method
The efficacy of Epcoritamab monotherapy will be centrally evaluated by the best CRR, defined as the proportion of patients who achieve a best response of CR after 3 cycles of Epcoritamab administration		The efficacy of Epcoritamab monotherapy will be centrally evaluated by the best CRR, defined as the proportion of patients who achieve a best response of CR after 3 cycles of Epcoritamab administration
The efficacy of Epcoritamab monotherapy and combination therapy with tafasitamab-lenalidomide will be evaluated by local investigators and central evaluation as per CRR (locally evaluated for Epcoritamab monotherapy; local and central evaluation for combination therapy), ORR, DoR, DoCR, Event-free survival (EFS), PFS and OS at any time		The efficacy of Epcoritamab monotherapy and combination therapy with tafasitamab-lenalidomide will be evaluated by local investigators and central evaluation as per CRR (locally evaluated for Epcoritamab monotherapy; local and central evaluation for combination therapy), ORR, DoR, DoCR, Event-free survival (EFS), PFS and OS at any time
The efficacy of Epcoritamab monotherapy and combination therapy with tafasitamab-lenalidomide will be evaluated by MRD (positive or negative) from ctDNA samples immediately before initiation of C3, C4, C7, C10, C12, C13, C15, End of Treatment (EoT) and cycles 18/24 (epcoritamab monotherapy) or cycles 21/27 (combination therapy).		The efficacy of Epcoritamab monotherapy and combination therapy with tafasitamab-lenalidomide will be evaluated by MRD (positive or negative) from ctDNA samples immediately before initiation of C3, C4, C7, C10, C12, C13, C15, End of Treatment (EoT) and cycles 18/24 (epcoritamab monotherapy) or cycles 21/27 (combination therapy).
The PFS, OS and DoR of patients with negative MRD at Visit 3 (V3) (immediately before administrating C3 of Epcoritamab monotherapy), as previously defined in this section		The PFS, OS and DoR of patients with negative MRD at Visit 3 (V3) (immediately before administrating C3 of Epcoritamab monotherapy), as previously defined in this section
The safety and tolerability of Epcoritamab monotherapy and combination therapy with tafasitamab-lenalidomide are evaluated as follows: Type, frequency, and severity of adverse events		The safety and tolerability of Epcoritamab monotherapy and combination therapy with tafasitamab-lenalidomide are evaluated as follows: Type, frequency, and severity of adverse events

Trial Locations

Locations (15): Hospital Universitario Central De Asturias
🇪🇸
Oviedo, Spain
Hospital Universitario Miguel Servet
🇪🇸
Zaragoza, Spain
University Clinical Hospital Virgen De La Arrixaca
🇪🇸
Murcia, Spain
Hospital Universitario Fundacion Jimenez Diaz
🇪🇸
Madrid, Spain
Hospital Germans Trias I Pujol
🇪🇸
Badalona, Spain
Hospital Universitari Vall D Hebron
🇪🇸
Barcelona, Spain
Hospital Universitario De Burgos
🇪🇸
Burgos, Spain
Hospital Universitario Basurto
🇪🇸
Bilbao, Spain
Hospital Universitario Y Politecnico La Fe
🇪🇸
Valencia, Spain
Hospital Universitario Infanta Leonor
🇪🇸
Madrid, Spain
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Hospital Universitario Central De Asturias
🇪🇸Oviedo, Spain
Angel Ramirez Payer
Site contact
985108000
apayer.angel@gmail.com