Study of Epcoritamab as a Consolidation Therapy in CLL/SLL

NCT07108998 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: UCCC-HEM-24-01IST-EPCO-00035
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 2 study of Epcoritamab as a consolidation therapy for 2nd generation BTKi +/- Obinutuzumab in CLL/SLL patients or patients with variants of this.

Conditions

CLL/SLL; CLL; SLL; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Small Lymphocytic Lymphoma Variant; Chronic Lymphocytic Leukemia Variants

Keywords

Epcoritamab; Obinutuzumab

Outcome Measures

Primary Outcomes (1)

• uMRD CR as defined by negative leukemia cells to the 10^6

  uMRD CR as defined by negative leukemia cells to the 10\^6 after 12 cycles of consolidative therapy with epcoritamab measured by Adaptive's NGS MRD assay (ClonoSEQ) in patients who have attained a partial response or better with detectable disease after acalabrutinib or zanubrutinib +/- obinutuzumab treatment for a minimum of 12 cycles of therapy

  Post 12 cycles (approximately 336 days after the start of first cycle) of consolidative therapy with epcoritamab

Secondary Outcomes (5)

• Safety measured by CTCAE v. 5.

  Day 1 of Cycle 1 to 60 days after end of C12D28 (i.e., approximately 396 days after the start of intervention)

• uMRD CR defined by negative leukemia cells to the 10^6 using NGG ClonoSEQ

  Post 6 cycles (approximately 196 days after start of intervention) of consolidation with epcoritamab.

• T-cell subsets levels measured by flow-cytometry

  Baseline, pre-treatment on Cycle1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 7 Day 1 and end of Cycle 12. Each cycle is 28 days.

• PFS defined as the interval between the first treatment day to the first sign of disease progression or death from any cause of patient

  Post 12 cycles of consolidative epcoritamab (approximately 364 days from start of intervention).. Each cycle is 28 days.

• OS defined as time from starting treatment until death of patients

  Post 12 cycles of consolidative epcoritamab (approximately 364 days from start of intervention).. Each cycle is 28 days.

Other Outcomes (5)

• T-cell cytotoxicity against primary pretreatment CLL cells

  Baseline, Day 1, Day 8, Day 29 of Cycle 1, end of Cycle 3, Cycle 6 and Cycle 12 of consolidation with epcoritamab. Each cycle is 28 days.

• T-cell proliferation against primary pretreatment CLL cells

  Baseline, Day 1, Day 8, Day 29 of Cycle 1, end of Cycle 3, Cycle 6 and Cycle 12 of consolidation with epcoritamab. Each cycle is 28 days.

• Cytokine production against autologous CLL cells

  Baseline, Day 1, Day 8, Day 29 of Cycle 1, end of Cycle 3, Cycle 6 and Cycle 12 of consolidation with epcoritamab. Each cycle is 28 days.

Study Arms (1)

Epcoritamab + SOC

EXPERIMENTAL

Epcoritamab is the investigational product under study in combination with SOC drugs in this protocol. During C1, epcoritamab will be initiated using step-up dosing (SUD) C1D1 .16mg, C1D8 .8mg, C1D15 3 mg, C1D22 24 mg vs 48 mg (full dose) during safety lead in to determine the RP2D. On Cycles 2-3 the RP2D (24mg vs 48 mg) will be administered on Days 1, 8, 15, 22. Then Cycles 4-9 RP2D will be administered on Days 1 \& 15. Then Cycle 10-12 RP2D on Day 1 of each cycle. Epcoritamab is administered subcutaneously. The SOC BTKi are oral medications administered daily during the trial period.

Drug: Epcoritamab

Interventions

Epcoritamab DRUG

Epcoritamab is the investigational product under study in combination with SOC drugs in this protocol. During C1, epcoritamab will be initiated using step-up dosing (SUD) C1D1 .16mg, C1D8 .8mg, C1D15 3 mg, C1D22 24 mg vs 48 mg (full dose) during safety lead in to determine the RP2D. On Cycles 2-3 the RP2D (24mg vs 48 mg) will be administered on Days 1, 8, 15, 22. Then Cycles 4-9 RP2D will be administered on Days 1 \& 15. Then Cycle 10-12 RP2D on Day 1 of each cycle. Epcoritamab is administered subcutaneously. The SOC BTKi are oral medications administered daily during the trial period.

Epcoritamab + SOC

Eligibility Criteria

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

You may qualify if:

• Diagnosis of CLL or SLL meeting the established 2018 iwCLL diagnostic criteria or variant of CLL/SLL and has received a 2nd generation BTKi (acalabrutinib or zanubrutinib) +/- obinutuzumab for a minimum of 12 months as first line therapy.
• a) Note: Variation in flow cytometry is defined as patients who have atypical immunophenotyping for CLL (CD5 negative, CD23 negative or surface expression of CD79b that is bright ) but clinically behave like CLL (leukocytosis, lymphadenopathy and splenomegaly) and have the FISH/Cytogenetics translocations(del 13q, trisomy 12, Del11q) or genomic features (XPO1, NOTCH1, SF3B1, FBXW7, MYD88, BIRC3, TRAF3, NFKBIE, SAMHD1, POT1, HIST1H1E, CHD2, ZMYM3, EGR2 and others) that are suggestive of CLL.
• Attainment of Partial Response or greater with a 2nd generation BTKi (acalabrutinib or zanubrutinib) +/- obinutuzumab but detectable disease in blood or bone marrow by NGS ClonoSEQ.
• Age ≥18 years.
• ECOG performance status ≤2 (or Karnofsky ≥60%, see Appendix D).
• Patients must have adequate organ and marrow function as defined below:
• Absolute neutrophil count ≥1,000/mcL, unless if neutropenia is due to underlying CLL bone marrow disease.
• Hemoglobin ≥8 g/dl unless if related to underlying CLL Platelets ≥50,000/ µL unless if related to underlying CLL Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (excepting Gilbert's syndrome, who may have a bilirubin \> 1.5 × ULN, per discussion between the Investigator and the UC PI).
• AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN Glomerular filtration rate (GFR) Calculated GFR using CKD-EPI formula ≥ 30 (See Appendix E) or multiplying the estimate of GFR by an individual body surface area calculated using an appropriate formula and dividing by 1.73 m2.
• Women of childbearing potential and non-sterile males must practice at least 1 of the following methods of birth control with their partner(s) throughout the study and for 4 months after discontinuing study drug:
• Total abstinence from sexual intercourse as the preferred lifestyle of the patient; periodic abstinence is not acceptable.
• Surgically sterile partner(s) by vasectomy, bilateral orchiectomy, bilateral tubal ligation, bilateral oophorectomy, or hysterectomy.
• Intrauterine device.
• Hormonal contraceptives (oral, parenteral, vaginal ring or transdermal) for at least 1-month prior to study drug administration.
• Women of childbearing potential must have a negative pregnancy result as follows: At Screening on a serum sample obtained within 7 days prior to the first study drug administration. If a urine pregnancy test at any timepoint during the study is positive or indeterminate, a serum pregnancy test will be performed for confirmation.

You may not qualify if:

• Obtaining a CR or nodal PR with no detectable disease in blood or bone marrow after treatment with a 2nd generation BTKi (acalabrutinib or zanubrutinib) +/- obinutuzumab as assessed by Adaptive's NGS ClonoSEQ.
• Absence of CD20 expression on CLL cells at pre-treatment.
• Received any prior treatment ever with a CD3×CD20 bispecific antibody.
• Organ transplant recipients are excluded except those with no active graft versus host disease (GVHD) requiring treatment within 12 months of beginning treatment on study.
• Receipt of a live vaccine within 28 days prior to study treatment initiation.
• Autoimmune diseases requiring high dose immunosuppressives (e.g., above 20 mg prednisone daily).
• Central nervous system (CNS) disease(s) unless in the opinion of the investigator these would not preclude the patient from participation.
• Known hypersensitivity to any of the components of the treatment drugs (see Investigators Brochure for a list of components).
• Patients with active Richter's transformation.
• a. Note: the following will be eligible and not excluded: patients with accelerated phase or prolymphocytic progression
• Patients who have received prior radiation therapy (RT) unless in the opinion of the investigator the prior receipt of RT will not adversely impact the patient's ability to participate.
• Patients who require anti-coagulation with warfarin or equivalent Vitamin K antagonist.
• Major surgery within 14 days prior to the first dose of study drug.
• Patient has significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 180 days prior to the first dose of study drug, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification or left ventricular ejection fraction ≤ 40%.
• Pregnant women, those planning to become pregnant during the study, and/or breastfeeding women are ineligible for participation.

Sponsors & Collaborators

• Zulfa Omer: lead
• Genmab: collaborator

Study Sites (1)

University of Cincinnati

Cincinnati, Ohio, 45219, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

UCCC Clinical Trials Office

CONTACT

513-584-7698; cancer@uchealth.com

Zulfa Omer, MD

CONTACT

Study Design

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

Model Details: Single Group

Study Record Dates

• First Submitted: July 21, 2025
• First Posted: August 7, 2025
• Study Start: August 22, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2029
• Last Updated: January 6, 2026

Record last verified: 2026-01

Locations

US (1)