Outpatient Epcoritamab in Large B-cell Lymphoma

NCT06811272 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 25-006
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to measure the efficacy of the study drug, epcoritamab, in participants with relapsed/refractory large B-cell lymphoma.

Conditions

Relapsed Large B-cell Lymphoma; Refractory Large B-cell Lymphoma

Keywords

Non-Transplant Eligible; Second Line Therapy; DLBCL; HGBCL; Naïve large B-cell lymphoma; First Line Therapy

Outcome Measures

Primary Outcomes (2)

• Complete Response Rate (CRR) in first line cohort

  The CRR is defined as the proportion of subjects achieving an objective response of complete response (CR) according to the Lugano Classification, prior to start of another non-study anticancer therapy. CRR is based on the best overall response. CRR will be reported as a proportion, exact binomial confidence interval, and assessed using an exact binomial test.

  Day 1 until date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 12 months after initial dose of study treatment.

• 12-month progression free survival (PFS) in second line cohort

  The time from registration to the earlier of progression or death due to any cause and will be defined as the percent of patients alive and progression-free at 12 months. Participants alive without disease progression are censored at date of last disease evaluation.

  Day 1 until date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 12 months after initial dose of study treatment.

Secondary Outcomes (12)

• 12-month progression free survival (PFS) in first line cohort

  Day 1 to 24 months post treatment

• Complete Response Rate in second line cohort

  Day 1 to 24 months post treatment

• Overall Response Rate

  Day 1 to 24 months post treatment

• Median Duration of Response

  Date of first response to first documented disease progression or date of death from any cause, whichever came first, assessed up to 24 months post treatment

• Median Duration of Complete Response

  Date of complete response to first documented disease progression or date of death from any cause, whichever came first, assessed up to 24 months post treatment

Study Arms (2)

First Line

EXPERIMENTAL

Epcoritamab will be given as monotherapy on EPCO cycles 1 days 1, 8, 15, and 22, EPCO cycles 2 days 1, 8, 15, and 22, EPCO cycles 3-4 days 1 and 15, and EPCO cycles 3-8 days 1 and 15 as an injection under your skin (subcutaneous injection). Epcoritamab will be given with chemotherapy through the vein with steroid pills (prednisone) on EPCO-CHEMO cycles 1-4 day 1 and EPCO-CHEMO cycles 1-6 day 1 based on tumor response. There are three different chemotherapy regimens which are Epco-R-CVP, Epco-R-CHOP, and Epco-pola-R-CHP. Epco-R-CVP consists of epcoritamab, rituximab, cyclophosphamide, vincristine, and prednisone. Epco-R-CHOP consists of epcoritamab, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. Epco-pola-R-CHP consist of epcoritamab, polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone. You will receive dexamethasone which may provide relief for areas of the body that are inflamed during study treatment.

Drug: Epcoritamab; Drug: Rituximab combined with cyclophosphamide, vincristine, and prednisone; Drug: Rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone; Drug: Rituximab combined with polatuzumab, cyclophosphamide, doxorubicin, and prednisone

Second Line

EXPERIMENTAL

Epcoritamab will be given as an injection under the skin (subcutaneous injection) on cycle 1-3 days 1, 8, 15, and 22, cycle 4-9 days 1 and 15, and cycle 10 and onwards day 1. You will receive dexamethasone which may provide relief for areas of the body that are inflamed during study treatment.

Drug: Epcoritamab

Interventions

Epcoritamab DRUG

Bispecific IgG1 antibody

First Line; Second Line

Rituximab combined with cyclophosphamide, vincristine, and prednisone DRUG

Epco-R-CVP

First Line

Rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone DRUG

Epco-R-CHOP

First Line

Rituximab combined with polatuzumab, cyclophosphamide, doxorubicin, and prednisone DRUG

Epco-pola-R-CHP

First Line

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• First Line Cohort
• No prior systemic antineoplastic therapy for large B-cell lymphoma.
• Score of "frail" or "unfit" on Fondazione Italiana Linfomi simplified Geriatric Assessment (FIL sGA) (Appendix E).
• Second Line Cohort
• Relapsed or refractory disease treated with 1 prior systemic antineoplastic line of therapy that includes an anti-CD20 monoclonal antibody plus an anthracycline and/or an alkylating agent. Patients who have received more than 1 prior systemic antineoplastic line of therapy are not eligible.
• Not a candidate for high dose chemotherapy and autologous stem cell transplant per the treating investigator, or patient refusal of high dose chemotherapy and autologous transplant.
• Both Cohorts
• Participants must have large B-cell lymphoma of one of the following histologic subtypes by WHO criteria:
• Diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS)
• High grade B-cell lymphoma (HGBCL) with rearrangements of MYC and BCL2 and/or BCL6
• HGBCL NOS
• EBV+ DLBCL
• Primary mediastinal B-cell lymphoma
• T-cell/histiocyte rich LBCL
• Grade 3B follicular lymphoma

You may not qualify if:

• Participant must not have used an investigational drug or approved systemic lymphoma therapy within 28 days preceding the first dose of study drug. Steroids for lymphoma disease control are permitted but must be stopped at least 7 days prior to the first dose of study drug.
• Participants must not have received prior CD20/CD3 bispecific antibody.
• Participants must not have received prior autologous or allogeneic stem cell transplant.
• Participants must not have received prior anti-CD19 CAR T-cell therapy.
• Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia. At the discretion of the overall PI, participants with residual toxicities \> Grade 1 may be considered eligible if in the opinion of the overall PI the residual toxicity is not likely to interfere with the safety or efficacy assessment of the investigational regimen. For residual hematologic toxicities greater than Grade 1, see 3.1.7.
• Participants must not have known central nervous system involvement by lymphoma.
• Participants must not have a current life-threatening illness, medical condition, or organ system dysfunction (other than the disease under study) which, in the Investigator's opinion, could compromise the subject's safety or put the study at risk. Patients that have mild cognitive impairment or dementia are eligible per investigators' opinion.
• Participants must not have an uncontrolled active infection. Localized fungal infection of skin or nails are permitted.
• Participants must not have active uncontrolled autoimmune disease. Autoimmune disease under control with chronic systemic corticosteroids at a dose of 10 mg/day of prednisone or less, or equivalent corticosteroid, are eligible.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to epcoritamab. A history of an infusion reaction to CD20-directed therapy is not considered an allergic reaction.
• Women who are pregnant are excluded from this study because it is unknown if epcoritamab can cause embryo-fetal harm when administered to a pregnant woman. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with epcoritamab, breastfeeding should be discontinued if the mother is treated with epcoritamab on study.
• Participant must not have active uncontrolled HIV infection. Participants with HIV are eligible if disease is adequately controlled on an antiretroviral regimen that is in accordance with the current international AIDS Society guidelines, with adequate control defined by presence of both an undetectable viral load, a CD4 count \>350, no evidence of AIDS-defining illness (with the exception of a lymphoma diagnosis), and no active opportunistic infections (infections controlled on appropriate anti-infective therapy are permitted).
• Participant must not have active hepatitis B infection. Participants with positive HBV core antibody or HBV surface antigen at screening are eligible if HBV viral load is negative by PCR and they are on appropriate antiviral therapy.
• Participant must not have active hepatitis C infection. Participants with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained.
• Note: Participants with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing.

Sponsors & Collaborators

• Genmab: collaborator
• Massachusetts General Hospital: lead

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Newton-Wellesley Hospital

Newton, Massachusetts, 02462, United States

RECRUITING

MeSH Terms

Interventions

Cyclophosphamide; Vincristine; Prednisone; Doxorubicin

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Julie E. Haydu, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Julie E. Haydu, MD, PhD

CONTACT

617-724-4000; julie_haydu@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 31, 2025
• First Posted: February 6, 2025
• Study Start: June 5, 2025
• Primary Completion: October 1, 2026
• Study Completion (Estimated): October 1, 2028
• Last Updated: August 13, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (2)