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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion Geltamo

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

4 Aug 2025 → ongoing

Decision date (initial)

2025-05-14

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Abbvie

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

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

Secondary objectives 5

1. To evaluate the efficacy of Epcoritamab monotherapy by central evaluation as second line treatment for LBCL patients after 3 cycles of administration.
2. To further evaluate the efficacy (local and central evaluation) of Epcoritamab monotherapy and combination therapy with tafasitamab-lenalidomide as second line treatment for LBCL patients adapted to early response by evaluating the CRR, ORR, DoR, Duration of complete response (DoCR) and survival endpoints
3. To further evaluate the efficacy of Epcoritamab monotherapy and combination therapy with tafasitamab-lenalidomide in second line treatment for LBCL patients adapted to early response assessed by MRD ctDNA during the first 12 complete cycles of treatment (monotherapy or combination) and cycles 18/24 (epcoritamab monotherapy) or cycles 21/27 (combination therapy)
4. To assess the impact of negative MRD before cycle 3 of Epcoritamab monotherapy in relation to PFS, OS, and DoR
5. To evaluate the safety and tolerability of Epcoritamab monotherapy and combination therapy with tafasitamab-lenalidomide when administered as second line treatment for LBCL patients adapted to early response

Conditions and MedDRA coding

Relapse/Refractory Large B Cell Lymphoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Written informed consent must be obtained before any study-specific assessment is performed.
2. Age >18 years
3. 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
4. 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
5. 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
6. Patients must be autologous stem cell transplantation (ASCT)-ineligible: Age ≥65 and/or HTC-CI ≥3 or or unwilling to receive transplant
7. PET positive disease
8. Performance status according to Eastern Cooperative Oncology Group (ECOG) 0 to 2.
9. 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.
10. 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.
11. 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
12. 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.
13. 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
14. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
15. Not included in other clinical trial or treated with an experimental drug

Exclusion criteria 18

1. Patients who received more than one prior line of systemic therapy
2. Patients with detectable Central Nervous System (CNS) lymphoma
3. 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%
4. Serious accompanying disorder leading to impaired organ function causing significant clinical problems and reduced life expectancy of less than 3 months
5. 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
6. 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%.
7. 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
8. Previous ASCT
9. Prior anti-CD3 and CD20 bispecific antibodies therapy or prior treatment with tafasitamab.
10. Presence of severe infection that is uncontrolled or requiring IV antimicrobials for management
11. 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.
12. Females who are pregnant or breastfeeding
13. Richter’s transformation or prior chronic lymphocytic leukemia (CLL).
14. 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
15. Recent major surgery (within 4 weeks before the start of Cycle 1 Day 1) other than for diagnosis
16. Vaccination with a live vaccine or COVID-19 vaccination within 4 weeks prior to treatment
17. 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
18. Close affiliation with the investigator (e.g. a close relative) or persons working at the study site

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 endpoints 5

1. 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
2. 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
3. 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).
4. 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
5. The safety and tolerability of Epcoritamab monotherapy and combination therapy with tafasitamab-lenalidomide are evaluated as follows: Type, frequency, and severity of adverse events

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion Geltamo

Sponsor organisation

Fundacion Geltamo

Address

Avenida Valdecilla Sn

City

Santander

Postcode

39008

Country

Spain

Scientific contact point

Organisation

Fundacion Geltamo

Contact name

Ana María Méndez López

Public contact point

Organisation

Fundacion Geltamo

Contact name

Ana María Méndez López

Locations

1 EU/EEA country · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications