Epcoritamab in Combination With Loncastuximab Tesirine in Relapsed/Refractory Large B-cell Lymphoma

NCT06919939 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 20241140
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether combining Loncastuximab Tesirine with Epcoritamab is tolerable and effective for reducing and/or eliminating lymphoma cells in the body.

Conditions

Large B-cell Lymphoma; Relapse

Outcome Measures

Primary Outcomes (5)

• Number of Participants Experiencing Cytokine Release Syndrome (CRS)-related Toxicity after Epcoritamab Administration

  The number of participants experiencing Cytokine Release Syndrome (CRS) toxicity associated with Epcoritamab therapy will be reported, including Grades 2, 3 and 4. CRS-related toxicity will be assessed according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria.

  Up to 14 months

• Number of Participants Experiencing Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS)-related Toxicity

  The number of participants experiencing Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS)-related toxicity including Grades 2, 3 and 4. ICANS-related toxicity will be assessed according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria.

  Up to 14 months

• Number of Participants Experiencing Neurologic Toxicities Associated with Epcoritamab

  The number of participants experiencing neurologic toxicities associated with Epcoritamab therapy will be reported, including Grades 2, 3 and 4. Neurologic toxicities will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion.

  Up to 14 months

• Number of Participants Experiencing Fluid Accumulation Associated with Loncastuximab

  The number of participants experiencing fluid accumulation associated with Loncastuximab therapy will be reported, including Grades 2, 3 and 4. Fluid accumulation toxicities will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion.

  Up to 31 weeks

• Number of Participants Experiencing Hepatotoxicity Associated with Loncastuximab

  The number of participants experiencing hepatotoxicity (liver-related toxicity) associated with Loncastuximab therapy including Grades 2, 3 and 4 toxicity. Hepatotoxicity will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion.

  Up to 31 weeks

Secondary Outcomes (4)

• Overall Response Rate (ORR)

  Up to 36 months

• Partial Metabolic Response (PMR) Rate

  Up to 36 months

• Progression-Free Survival (PFS)

  Up to 36 months

• Overall Survival (OS)

  Up to 36 months

Study Arms (1)

EPCOR in combination with LONCA Treatment Group

EXPERIMENTAL

Participants in the Epcoritamab (EPCOR) in combination with Loncastuximab (LONCA) treatment group will receive up to 4 cycles of combination EPCOR and LONCA therapy, and an additional 8 cycles of EPCOR therapy, for a total of twelve treatment cycles. Cycles 1 through 3 last 21 days each; cycles four through 12 last 28 days each. Protocol therapy will last approximately 12 months. Total participation duration is approximately 3 years.

Drug: Epcoritamab; Drug: Loncastuximab Tesirine

Interventions

Epcoritamab DRUG

Epcoritamab will be administered via subcutaneous injection at the following dose levels and schedule over a total of twelve cycles: * Cycle 1 Day 1: Step-up dose of 0.16 mg * Cycle 1 Day 8: Step-up dose of 0.80 mg * Cycle 1 Day 15: First full dose of 48 mg. * Cycles 2 through 4 Days 1, 8 and 15: 48 mg * Cycles 5 through 12 Days 1 and 15: 48 mg

Also known as: Epkinly

EPCOR in combination with LONCA Treatment Group

Loncastuximab Tesirine DRUG

Loncastuximab will be administered intravenously (IV) at the following dose level and schedule over a total of four cycles: * Cycles 1 and 2 Day 1: 120 mcg/kg * Cycles 3 and 4 Day 1: 75 mcg/kg * Cycle 4 Day 22: 75 mcg/kg

Also known as: Loncatuximab, Zynlonta

EPCOR in combination with LONCA Treatment Group

Eligibility Criteria

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

You may qualify if:

• Men and women aged 18 years or older at the time of signing informed consent.
• Able and willing to sign the informed consent form (ICF).
• Ability to comply with the trial protocol.
• Relapsed/refractory (r/r) large B-cell lymphoma (LBCL) as determined by the local hematopathology laboratory from the following diagnoses by 2016 World Health Organization (WHO) classification of lymphoid neoplasms (Swerdlow et al., 2016):
• LBCL or DLBCL, not otherwise specified (NOS)
• High-grade B-cell lymphoma (NOS or double/triple hit \[technically classified in WHO 2016 as high-grade B-cell lymphoma (HGBCL), with Myc and B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) translocations\])
• Transformed from follicular lymphoma, marginal zone lymphoma (MZL), and nodular lymphocyte predominant Hodgkin lymphoma
• Follicular lymphoma stage 3B
• Primary mediastinal B-cell lymphoma previously treated with checkpoint inhibitor Note: Relapsed disease is defined as disease that has recurred ≥6 months after completion of therapy. Refractory disease is defined as disease that either progressed during therapy or progressed within 6 months (\<6 months) of completion of therapy.
• Participants who have received at least one prior systemic therapy for LBCL including anti-cluster of differentiation 20 (anti-CD20) monoclonal antibody and anthracycline-containing therapy.
• Measurable disease by 2014 Lugano Classification. (Participants who have measurable disease, defined as at least 1 bi-dimensionally measurable nodal lesion, defined as \>1.5 cm in its longest dimension, or at least 1 bi-dimensionally measurable extra nodal lesion, defined as \>1.0 cm in its longest dimension.)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2.
• Adequate hematologic, hepatic, and renal function tested within 6 weeks prior to the start of therapy (values must not be achieved with growth factors within 72 hs):
• Absolute neutrophil count (ANC) ≥ 1.0 × 10\^9 cells/L
• Hemoglobin ≥8.0 g/dL without blood transfusion in the past week

You may not qualify if:

• Primary central nervous system (CNS) lymphoma or known CNS involvement by lymphoma at screening as confirmed by magnetic resonance imaging (MRI)/computed tomography (CT) scan (brain) and, if clinically indicated, by lumbar puncture.
• Prior treatment with anti-cluster of differentiation 19 (anti-CD19) chimeric antigen receptor T-cell (CAR-T) therapy
• Prior exposure to bispecific T-cell engaging antiCD20XCD3 antibodies
• Prior autologous or allogenic stem cell transplant
• Known clinically significant pulmonary disease, including:
• Pulmonary fibrosis affecting patient's exercise tolerance.
• Chronic obstructive pulmonary disease (COPD) affecting patient's exercise tolerance.
• Known clinically significant cardiac disease, including:
• Onset of unstable angina pectoris within 6 months of signing ICF
• Acute myocardial infarction within 6 months of signing ICF
• Congestive heart failure (grade III or IV as classified by the New York Heart Association
• Pregnant or breast feeding
• Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy.
• Chronic or current active infectious disease (including severe acute respiratory syndrome (SARS) coronavirus 2 (CoV-2) requiring systemic antibiotics, antifungal, or antiviral treatment or any major episode of infection requiring treatment with intravenous (IV) antibiotics within 2 weeks of Day 1 of Cycle 1.
• Exposure to a live vaccine within 30 days of administration or anticipation that a live attenuated vaccine will be required during the study.

Sponsors & Collaborators

• University of Miami: lead
• ADC Therapeutics S.A.: collaborator
• Genmab: collaborator

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

RECRUITING

MeSH Terms

Conditions

Recurrence

Interventions

loncastuximab tesirine

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Juan Alderuccio, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Juan Alderuccio, MD

CONTACT

305-243-4372; jalderuccio@med.miami.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2025
• First Posted: April 9, 2025
• Study Start: January 7, 2026
• Primary Completion (Estimated): January 7, 2031
• Study Completion (Estimated): January 7, 2031
• Last Updated: March 2, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)