This is the classic website, which will be retired eventually. Please visit the modernized ClinicalTrials.gov instead.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome (EPCORE™ CLL-1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04623541
Recruitment Status : Recruiting
First Posted : November 10, 2020
Last Update Posted : April 3, 2024
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
Genmab

Tracking Information
First Submitted Date  ICMJE October 27, 2020
First Posted Date  ICMJE November 10, 2020
Last Update Posted Date April 3, 2024
Actual Study Start Date  ICMJE November 25, 2020
Estimated Primary Completion Date June 2029   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 9, 2023)
  • Dose Escalation Phase (R/R CLL arm): Number of Participants with Dose Limiting Toxicities (DLTs) [ Time Frame: During the first cycle for low dose cohorts (Cycle length = 28 days) and for high dose cohorts (Cycle length = 35 days) ]
    DLT events were defined as clinically significant adverse events (AEs) or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications as assessed per Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria version 5.0.
  • Dose Escalation Phase: Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: From first dose until the end of the safety follow-up period (60 days after last dose) ]
  • Dose Escalation Phase: Number of Participants with Cytokine Release Syndrome (CRS), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) and Clinical Tumor Lysis Syndrome (CTLS) [ Time Frame: From first dose until the end of the safety follow-up period (60 days after last dose) ]
    CRS and ICANS will be graded based on American Society for Transplantation and Cellular Therapy (ASTCT) criteria. CTLS will be graded according to Cairo-Bishop criteria.
  • Expansion Phase: Overall Response Rate (ORR) [ Time Frame: Up to 5 years ]
    ORR is defined as the percentage of participants who achieve a response of partial response or complete response, prior to initiation of subsequent therapy. R/R CLL participants will be assessed according to International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria and the RS participants according to Lugano criteria.
Original Primary Outcome Measures  ICMJE
 (submitted: November 5, 2020)
  • Dose escalation part: Incidence of dose limiting toxicities (DLTs) [ Time Frame: For each subject in a given dose escalation cohort, DLTs are assessed during the first cycle (28 days). ]
    To identify the recommended phase II dose (RP2D)
  • Dose escalation part: Incidence of dose limiting toxicities (DLTs) [ Time Frame: For each subject in a given dose escalation cohort, DLTs are assessed during the first cycle (28 days). ]
    To identify maximum tolerated dose (MTD) if reached
  • Dose expansion part: assess preliminary efficacy of epcoritamab [ Time Frame: response assessments will be evaluated evaluated on an ongoing basis during the conduct of the trial (up to 3 years after the last subject first dose) ]
    overall response rate
  • Dose escalation and expansion part: Adverse events (AEs) [ Time Frame: AEs are collected throughout trial until the end of the safety follow-up period (60 days after last dose) ]
    To assess the safety and tolerability of epcoritamab throughout the treatment period of patients participating in the trial)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 9, 2023)
  • Expansion Phase: Number of Participants with TEAEs and SAEs [ Time Frame: From first dose until the end of the safety follow-up period (60 days after last dose) ]
  • Dose Escalation Phase: ORR [ Time Frame: Up to 5 years ]
    ORR is defined as percentage of participants who achieve a response of partial response or complete response, prior to initiation of subsequent therapy as assessed by iwCLL criteria.
  • Both Phases: Duration of Response (DOR) [ Time Frame: Up to 5 years ]
    DOR is defined among responders, as the time from the initial documentation of response to the date of disease progression or death, whichever occurs earlier.
  • Both Phases: Number of Participants with Complete Remission (CR) / CR with Incomplete Bone Marrow Recovery (CRi) [ Time Frame: Up to 5 years ]
    CR and CRi for R/R CLL participants will be assessed according to iwCLL criteria and CR for the RS participants, according to Lugano criteria.
  • Both Phases: Time to Response (TTR) [ Time Frame: Up to 5 years ]
    TTR is defined among responders, as the time between first dose of epcoritamab and the initial documentation of response.
  • Both Phases: Progression Free Survival (PFS) [ Time Frame: Up to 5 years ]
    PFS is defined as the time from the first dosing date of epcoritamab and the date of disease progression or death, whichever occurs earlier.
  • Both Phases: Overall Survival (OS) [ Time Frame: Up to 5 years ]
    OS is defined as the time from the first dosing date of epcoritamab and the date of death due to any cause.
  • Both Phases: Time to Next Systemic Anti-cancer Therapy (TTNT) [ Time Frame: Up to 5 years ]
    TTNT is defined as the time from the first dosing date of epcoritamab to the first documented administration of subsequent systemic anticancer therapy.
  • Both Phases: Area Under the Concentration-time Curve (AUC) From Time Zero to Last Quantifiable Sample (AUClast) in Epcoritamab [ Time Frame: Predose and post dose at multiple timepoints at end of each cycle for low dose and high dose cohorts (Cycle length = 28 days, except Cycle 1 for high dose cohorts = 35 Days) ]
  • Both Phases: AUC From Time Zero to Infinity (AUCinf) in Epcoritamab [ Time Frame: Predose and post dose at multiple timepoints at end of each cycle for low dose and high dose cohorts (Cycle length = 28 days, except Cycle 1 for high dose cohorts = 35 Days) ]
  • Both Phases: Maximum (Peak) Plasma Concentration (Cmax) in Epcoritamab [ Time Frame: Predose and post dose at multiple timepoints at end of each cycle for low dose and high dose cohorts (Cycle length = 28 days, except Cycle 1 for high dose cohorts = 35 Days) ]
  • Both Phases: Pre-dose (Trough) Concentrations (Cthrough) in Epcoritamab [ Time Frame: Predose and post dose at multiple timepoints at end of each cycle for low dose and high dose cohorts (Cycle length = 28 days, except Cycle 1 for high dose cohorts = 35 Days) ]
  • Both Phases: Time to Reach Cmax (Tmax) in Epcoritamab [ Time Frame: Predose and post dose at multiple timepoints at end of each cycle for low dose and high dose cohorts (Cycle length = 28 days, except Cycle 1 for high dose cohorts = 35 Days) ]
  • Both Phases: Elimination Half-life (T1/2) in Epcoritamab [ Time Frame: Predose and post dose at multiple timepoints at end of each cycle for low dose and high dose cohorts (Cycle length = 28 days, except Cycle 1 for high dose cohorts = 35 Days) ]
  • Both Phases: Total Body Clearance of Drug From Plasma (CL) in Epcoritamab [ Time Frame: Predose and post dose at multiple timepoints at end of each cycle for low dose and high dose cohorts (Cycle length = 28 days, except Cycle 1 for high dose cohorts = 35 Days) ]
  • Both Phases: Volume of distribution (Vd) in Epcoritamab [ Time Frame: Predose and post dose at multiple timepoints at end of each cycle for low dose and high dose cohorts (Cycle length = 28 days, except Cycle 1 for high dose cohorts = 35 Days) ]
  • Both Phases: Lymphoid Cells for Immunophenotyping [ Time Frame: Up to 5 years ]
    Evaluation of B cells, T cells and their activation
  • Expansion Phase: Number of Participants with CRS, ICANS and CTLS [ Time Frame: From first dose until the end of the safety follow-up period (60 days after last dose) ]
    CRS and ICANS will be graded based on ASTCT criteria. CTLS will be graded according to Cairo-Bishop criteria.
  • Expansion Phase: Percentage of Participants with Minimal Residual Disease (MRD) Negativity [ Time Frame: Up to 5 years ]
    MRD negativity rate, is defined as the proportion of participants with at least 1 undetectable MRD result according to the specific threshold, prior to initiation of subsequent therapy.
  • Both Phases: Number of Participants with Anti-drug Antibodies (ADA) to Epcoritamab [ Time Frame: Up to end of treatment period (Up to 2 years) ]
  • Expansion Phase: Number of Participants with Partial Remission (PR)/Nodular Partial Remission (nPR) [ Time Frame: Up to 5 years ]
    nPR is defined as PR with residual nodules or suspicious lymphocytic infiltrates in participants who are in remission. nPR is only calculated for R/R CLL.
  • Both Phases: Duration of MRD Negativity [ Time Frame: Up to 5 years ]
    The time from first achieving MRD negativity after start of treatment to the MRD conversion to positive.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 5, 2020)
  • Dose escalation and expansion part: To characterize the pharmacokinetic properties of epcoritamab [ Time Frame: assessed through trial until the end of the treatment period, expected average of 1 year ]
    Pharmacokinetic (PK) parameters Clearance (Cl)
  • Dose escalation and expansion part: To characterize the pharmacokinetic properties of epcoritamab [ Time Frame: assessed through trial until the end of the treatment period, expected average of 1 year ]
    PK parameters Volume of Distrubution (Vd)
  • Dose escalation and expansion part: To characterize the pharmacokinetic properties of epcoritamab [ Time Frame: assessed through trial until the end of the treatment period, expected average of 1 year ]
    PK parameters maximum (peak) plasma drug concentration (Cmax)
  • Dose escalation and expansion part: To characterize the pharmacokinetic properties of epcoritamab [ Time Frame: assessed through trial until the end of the treatment period, expected average of 1 year ]
    PK parameters time to reach maximum (peak) plasma concentration (Tmax)
  • Dose escalation and expansion part: To characterize the pharmacokinetic properties of epcoritamab [ Time Frame: assessed through trial until the end of the treatment period, expected average of 1 year ]
    PK parameters Area under the concentration-time curve (AUC) from time zero to last quantifiable sample
  • Dose escalation and expansion part: To characterize the pharmacokinetic properties of epcoritamab [ Time Frame: assessed through trial until the end of the treatment period, expected average of 1 year ]
    PK parameters Area under the concentration-time curve (AUC) from time zero to infinity
  • Dose escalation and expansion part: To characterize the pharmacokinetic properties of epcoritamab [ Time Frame: assessed through trial until the end of the treatment period, expected average of 1 year ]
    PK parameters pre-dose (trough) concentrations
  • Dose escalation and expansion part: To characterize the pharmacokinetic properties of epcoritamab [ Time Frame: assessed through trial until the end of the treatment period, expected average of 1 year ]
    PK parameters elimination half-life (T1/2)
  • Dose escalation and expansion part: To evaluate pharmacodynamic markers of epcoritamab [ Time Frame: assessed through trial until the end of the treatment period, expected average of 1 year ]
    pharmacodynamic (PD) marker cytokines
  • Dose escalation and expansion part: To evaluate pharmacodynamic markers of epcoritamab [ Time Frame: assessed through trial until the end of the treatment period, expected average of 1 year ]
    pharmacodynamic (PD) marker immune subset CD4
  • Dose escalation and expansion part: To evaluate pharmacodynamic markers of epcoritamab [ Time Frame: assessed through trial until the end of the treatment period, expected average of 1 year ]
    pharmacodynamic (PD) marker immune subset CD8
  • Dose escalation and expansion part: To evaluate pharmacodynamic markers of epcoritamab [ Time Frame: assessed through trial until the end of the treatment period, expected average of 1 year ]
    pharmacodynamic (PD) marker immune subset B cells
  • Dose escalation and expansion part: To evaluate pharmacodynamic markers of epcoritamab [ Time Frame: assessed through trial until the end of the treatment period, expected average of 1 year ]
    pharmacodynamic (PD) marker immune subset activation marker positive/expression level
  • Dose escalation and expansion part: Evaluate the immunogenicity of epcoritamab [ Time Frame: assessed through trial until the end of the treatment period, expected average of 1 year ]
    incidence of antidrug-antibodies to epcoritamab
  • Dose escalation part: Assess the preliminary anti-tumor activity of epcoritamab [ Time Frame: response assessments will be evaluated evaluated on an ongoing basis during the conduct of the trial (up to 3 years after the last subject first dose) ]
    overall response rate
  • Dose escalation and expansion part: Assess the preliminary anti-tumor activity of epcoritamab [ Time Frame: response assessments will be evaluated evaluated on an ongoing basis during the conduct of the trial (up to 3 years after the last subject first dose) ]
    duration of response
  • Dose escalation and expansion part: Assess the preliminary anti-tumor activity of epcoritamab [ Time Frame: response assessments will be evaluated evaluated on an ongoing basis during the conduct of the trial (up to 3 years after the last subject first dose) ]
    time to response
  • Dose escalation and expansion part: Assess the preliminary anti-tumor activity of epcoritamab [ Time Frame: response assessments will be evaluated evaluated on an ongoing basis during the conduct of the trial (up to 3 years after the last subject first dose) ]
    progression free survival
  • Dose escalation and expansion part: Assess the preliminary anti-tumor activity of epcoritamab [ Time Frame: response assessments will be evaluated evaluated on an ongoing basis during the conduct of the trial (up to 3 years after the last subject first dose) ]
    overall survival
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome
Official Title  ICMJE A Phase 1b/2, Open-Label, Safety and Efficacy Study of Epcoritamab (GEN3013; DuoBody®-CD3xCD20) in Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome
Brief Summary

The study is a global, multi-center safety and efficacy trial of epcoritamab, an antibody also known as EPKINLY™ and GEN3013 (DuoBody®-CD3xCD20). Epcoritamab will either be studied as:

  • Monotherapy, or
  • Combination therapy:

    • epcoritamab + venetoclax
    • epcoritamab + lenalidomide
    • epcoritamab + R-CHOP (i.e., rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine and prednisone).

The study includes patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL)/small lymphocytic lymphoma (SLL) and patients with Richter's Syndrome (RS).

Study participants with R/R CLL/SLL are treated either with epcoritamab as monotherapy or epcoritamab + venetoclax. Study participants with RS are treated either with epcoritamab as monotherapy or epcoritamab + lenalidomide or epcoritamab + R-CHOP. The trial consists of two parts, a dose-escalation phase (phase Ib) and an expansion phase (phase II). Patients with RS are only included in the expansion phase.

Detailed Description

The purpose of the dose-escalation phase of the trial is to determine the recommended phase 2 dose (RP2D) and the maximum tolerated dose (MTD; if reached) as well as establish the safety profile of epcoritamab monotherapy and epcoritamab + venetoclax in participants with R/R CLL.

The purpose of the expansion phase is to assess and evaluate the preliminary efficacy, safety and tolerability profiles of epcoritamab monotherapy and epcoritamab + venetoclax at the RP2D for patients with R/R CLL/SLL. Along with this, epcoritamab monotherapy, epcoritamab + lenalidomide and epcoritamab + R-CHOP will be evaluated in patients with RS to assess their efficacy, safety and tolerability profiles.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Relapsed/Refractory Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
  • Richter's Syndrome
Intervention  ICMJE
  • Biological: Epcoritamab
    Epcoritamab will be administered subcutaneously in cycles of 28 days (except Cycle 1 for high-dose cohorts = 35 days).
    Other Names:
    • EPKINLY™
    • GEN3013
    • DuoBody®-CD3xCD20
  • Biological: Epcoritamab
    Epcoritamab will be administered subcutaneously in cycles of 21 days (Cycle 1-6) and 28 days for Cycle 7 and beyond.
    Other Names:
    • EPKINLY™
    • GEN3013
    • DuoBody®-CD3xCD20
  • Drug: rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone
    R-CHOP will be administered intravenously in cycles of 21 days for the first 6 cycles.
  • Drug: Venetoclax
    Venetoclax tablets will be administered orally once daily during the 5-week ramp up period and during Cycle 1-26 of 28 or 35 days each.
  • Biological: Epcoritamab
    Epcoritamab will be administered subcutaneously in cycles of 28 days.
    Other Names:
    • EPKINLY™
    • GEN3013
    • DuoBody®-CD3xCD20
  • Drug: Lenalidomide
    Lenalidomide capsules will be administered once daily for 21 days in each cycle of 28 days up to 12 cycles.
Study Arms  ICMJE
  • Experimental: Epcoritamab in R/R CLL/SLL
    In both study phases. Participants in the expansion phase will be treated at the RP2D defined in the dose-escalation phase.
    Intervention: Biological: Epcoritamab
  • Experimental: Epcoritamab in RS
    Only in expansion phase.
    Intervention: Biological: Epcoritamab
  • Experimental: Epcoritamab + Venetoclax in R/R CLL/SLL
    In both study phases. Participants in the expansion phase will be treated at the RP2D defined in the dose-escalation phase.
    Interventions:
    • Biological: Epcoritamab
    • Drug: Venetoclax
  • Experimental: Epcoritamab + Lenalidomide in RS
    Only in expansion phase.
    Interventions:
    • Biological: Epcoritamab
    • Drug: Lenalidomide
  • Experimental: Epcoritamab + R-CHOP in RS
    Only in expansion phase.
    Interventions:
    • Biological: Epcoritamab
    • Drug: rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 9, 2023)
184
Original Estimated Enrollment  ICMJE
 (submitted: November 5, 2020)
32
Estimated Study Completion Date  ICMJE August 2029
Estimated Primary Completion Date June 2029   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria

  1. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
  2. Evidence of CD20 positivity in a sample representative of the disease at Screening.
  3. Acceptable hematology parameters and organ function based on baseline bloodwork.
  4. For R/R CLL arms - Must have active CLL/SLL disease requiring treatment per iwCLL 2018 criteria.
  5. For R/R CLL arms - Received at least 2 prior lines of systemic anti-neoplastic therapy including a Bruton's tyrosine kinase (BTK) inhibitor.
  6. For all RS arms - Have tumor biopsy-proven CD20+ Diffuse large B-cell Lymphoma (DLBCL) and a clinical history of CLL/SLL.
  7. For all RS arms - Must have measurable disease by fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) or magnetic resonance imaging (MRI) scan.
  8. For all RS arms - Must provide mandatory formalin-fixed, paraffin-embedded (FFPE) tumor biopsy sample.
  9. Life expectancy >3 months on standard of care (SOC).
  10. For RS - monotherapy arm: Deemed as ineligible for chemoimmunotherapy at investigator's discretion or participant who refuses to receive intensive chemotherapy
  11. For RS - lenalidomide combination therapy arm

    • Deemed as ineligible for chemoimmunotherapy at the investigator's discretion, or participant who refuses to receive intensive chemotherapy.
    • Eligible for treatment with lenalidomide.
    • Must be willing to use contraception and adhere to the Lenalidomide Pregnancy Risk Minimization Plan
  12. For RS - R-CHOP combination Therapy Arm -

    • Eligible for treatment with R-CHOP.
  13. For R/R CLL - venetoclax combination Therapy arm - after receiving at least 1 prior line of systemic antineoplastic therapy.

Key Exclusion Criteria

  1. Received prior treatment with a CD3×CD20 bispecific antibody.
  2. Received any prior allogeneic hematopoietic stem cell transplantation (HSCT) or solid organ transplantation.
  3. Received (CAR) T-cell therapy within 100 days or an investigational drug within 4 weeks, prior to first dose of epcoritamab.
  4. Autoimmune disease or other diseases that require permanent or high-dose immunosuppressive therapy.
  5. Received vaccination with live vaccines within 28 days.
  6. Clinically significant cardiac disease.
  7. Known current malignancy other than inclusion diagnosis.
  8. Has had major surgery within 4 weeks.
  9. Active hepatitis B virus or active hepatitis C.
  10. Known history of HIV.
  11. For R/R CLL arms - Any history of RS or evidence indicating a potential Richter's transformation.
  12. Received venetoclax within 24 months prior to beginning venetoclax ramp-up for this trial and progressed on treatment.
  13. For all RS arms - Diagnosis of Richter's syndrome not of the DLBCL subtype such as Hodgkin's lymphoma, prolymphocytic leukemia.
  14. RS - Lenalidomide Combination Therapy and RS Monotherapy Arms - received more than 2 prior lines of therapy for RS.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Genmab Trial Information +4570202728 clinicaltrials@genmab.com
Listed Location Countries  ICMJE Australia,   Belgium,   Czechia,   Denmark,   France,   Germany,   Israel,   Italy,   Netherlands,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04623541
Other Study ID Numbers  ICMJE GCT3013-03
2020-000848-57 ( EudraCT Number )
NL74221.056.20 ( Registry Identifier: CCMO )
MOH_2023-04-02_012496 ( Registry Identifier: MyTrial )
2023-504828-25-00 ( Registry Identifier: EU CTIS )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Genmab
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Genmab
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE AbbVie
Investigators  ICMJE Not Provided
PRS Account Genmab
Verification Date April 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP