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EPCORE CLL-1: Safety & Efficacy Study of Epcoritamab in Subjects With R/R Chronic Lymphocytic Leukemia and Richter's Syndrome

Sponsor
Genmab (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04623541
Collaborator
AbbVie (Industry)
102
Enrollment
23
Locations
2
Arms
68
Anticipated Duration (Months)
4.4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The trial is an open-label, multi-center safety and efficacy trial of epcoritamab in relapsed/refractory chronic lymphocytic leukemia (R/R CLL) and Ritcher's Syndrome (RS). The trial consists of two parts, a dose escalation phase (phase Ib) and an expansion phase (phase II).

Condition or Disease Intervention/Treatment Phase
  • Biological: Epcoritamab
 Phase 1/Phase 2

Detailed Description

The purpose of the 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 in patients with R/R CLL.

In the expansion phase, additional patients will be treated with epcoritamab at the RP2D and the purpose is to assess and evaluate the preliminary efficacy, safety and tolerability profiles of epcoritamab at the RP2D for R/R CLL and RS.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
102 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1b/2, Open-Label, Safety and Efficacy Study of Epcoritamab (GEN3013; DuoBody®-CD3 X CD20) in Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome
Actual Study Start Date :
Nov 30, 2020
Anticipated Primary Completion Date :
Aug 1, 2024
Anticipated Study Completion Date :
Aug 1, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: Epcoritamab in R/R CLL

R/R CLL: in both dose escalation and dose expansion phases. Patients in the dose expansion phase will be treated at the RP2D defined in the dose escalation phase.

Biological: Epcoritamab
Epcoritamab will be administered subcutaneously (SC) in cycles of 28 days.
Other Names:
  • GEN3013; DuoBody®-CD3xCD20

    		•
    Experimental: Epcoritamab in RS

    RS: only in dose expansion phase. Patients in the dose expansion phase will be treated at the RP2D defined in the dose escalation phase.

    Biological: Epcoritamab
    Epcoritamab will be administered subcutaneously (SC) in cycles of 28 days.
    Other Names:
  • GEN3013; DuoBody®-CD3xCD20

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Dose escalation phase: Incidence of dose limiting toxicities (DLTs) [For each subject in a given cohort, DLTs are assessed during the first cycle (28 days)]

      To identify the RP2D and the MTD, if reached

    2. Dose escalation phase: Incidence of Adverse Events (AEs) [From first dose until the end of the safety follow-up period (60 days after last dose)]

      To assess the safety and tolerability of epcoritamab

    3. Dose expansion phase: Overall response rate (ORR) [From first dose until up to 3 years after the last subject's first dose]

      To evaluate the preliminary anti-tumor activity of epcoritamab

    Secondary Outcome Measures

    1. Dose expansion phase: Incidence of AEs [From first dose until the end of the safety follow-up period (60 days after last dose)]

      To assess the safety and tolerability of epcoritamab

    2. Dose escalation phase: ORR [From first dose until up to 3 years after the last subject's first dose]

      To evaluate the preliminary anti-tumor activity of epcoritamab

    3. Both phases: Duration of response (DOR) [From first dose until up to 3 years after the last subject's first dose]

      To evaluate the preliminary anti-tumor activity of epcoritamab

    4. Both phases: Complete remission (CR) / CR with incomplete bone marrow recovery (CRi) [Throughout the conduct of the trial (up to 3 years after the last subject first dose)]

      To evaluate the preliminary anti-tumor activity of epcoritamab. CRi only calculated for R/R CLL

    5. Both phases: Time to response (TTR) [From first dose until up to 3 years after the last subject's first dose]

      To evaluate the preliminary anti-tumor activity of epcoritamab

    6. Both phases: Progression free survival (PFS) [From first dose until up to 3 years after the last subject's first dose]

      To evaluate the preliminary anti-tumor activity of epcoritamab

    7. Both phases: Overall survival (OS) [From first dose until up to 3 years after the last subject's first dose]

      To evaluate the preliminary anti-tumor activity of epcoritamab

    8. Dose expansion part: Time to next systemic anti-cancer therapy (TTNT) [From first dose until up to 3 years after the last subject's first dose]

      To evaluate the preliminary anti-tumor activity of epcoritamab

    9. Both phases: Area under the concentration-time curve (AUC) from time zero to last quantifiable sample [From first dose until the end of the treatment period, expected average of 1 year]

      To characterize the pharmacokinetic (PK) properties of epcoritamab

    10. Both phases: AUC from time zero to infinity (AUCinf) [From first dose until the end of the treatment period, expected average of 1 year]

      To characterize the PK properties of epcoritamab

    11. Both phases: Maximum (peak) plasma drug concentration (Cmax) [From first dose until the end of the treatment period, expected average of 1 year]

      To characterize the PK properties of epcoritamab

    12. Both phases: Pre-dose (trough) concentrations (Cthrough) [From first dose until the end of the treatment period, expected average of 1 year]

      To characterize the PK properties of epcoritamab

    13. Both phases: Time to reach Cmax (Tmax) [From first dose until the end of the treatment period, expected average of 1 year]

      To characterize the PK properties of epcoritamab

    14. Both phases: Elimination half-life (T1/2) [From first dose until the end of the treatment period, expected average of 1 year]

      To characterize the PK properties of epcoritamab

    15. Both phases: Total body clearance of drug from plasma (CL) [From first dose until the end of the treatment period, expected average of 1 year]

      To characterize the PK properties of epcoritamab

    16. Both phases: Volume of distribution (Vd) [From first dose until the end of the treatment period, expected average of 1 year]

      To characterize the PK properties of epcoritamab

    17. Both phases: Lymphoid cells for immunophenotyping [From first dose until the end of the treatment period, expected average of 1 year]

      Evaluation of B cells, T cells and their activation

    18. Both phases: Cytokines [From first dose until the end of the treatment period, expected average of 1 year]

      To evaluate pharmacodynamic markers of epcoritamab

    19. Dose expansion phase: Incidence of minimal residual disease (MRD) negative status [From first dose until up to 3 years after the last subject's first dose]

      Peripheral blood and bone marrow aspirate

    20. Both phases: Incidence of antidrug-antibodies (ADA) to epcoritamab [From first dose until the end of the treatment period, expected average of 1 year]

      Evaluate the immunogenicity of epcoritamab

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Key Inclusion Criteria

    1. Subject must sign an ICF and be at least 18 years of age

    2. ECOG performance status score of 0, 1 or 2

    3. Screening evidence of CD20 positivity

    4. Has laboratory parameters - HBG-≥9.0 g/dL; ANC-≥1.0 x 109/L; Platelets-≥30 x 109/L

    5. Received a cumulative dose of corticosteroids less than the equivalent of 250 mg of prednisone within the 2-week period before the first dose

    6. Availability of fresh bone marrow material

    7. A woman must not be of childbearing potential and practicing a highly effective method of birth control, with a negative serum beta-hCG and urine pregnancy test at screening.

    8. A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control.

    9. For R/R CLL Cohort - Must have active CLL disease requiring treatment per iwCLL2018

    10. For R/R CLL Cohort - received at least 2 prior lines of systemic anti-neoplastic therapy anti-neoplastic therapy including a BTK inhibitor

    11. For R/R CLL Cohort - Measurable Disease ≥5 × 109/L (5,000/μL) B lymphocytes in peripheral blood or Presence of measurable lymphadenopathy and/or organomegaly

    12. For RS Cohort - Documented clinical history transformation to diffuse large B cell lymphoma (DLBCL)

    13. For RS Cohort - Not eligible for chemoimmunotherapy

    14. For RS Cohort - must have detectable disease by PET scan and measurable by CT scan or MRI

    Key Exclusion Criteria

    1. Received prior treatment with a CD3 × CD20 bispecific antibody.

    2. Received any prior allogeneic HSCT or solid organ transplantation.

    3. Received treatment with an anti-cancer biologic including anti-CD20 therapy, radio-conjugated or toxin-conjugated antibody or CAR T-cell therapy or investigational drug within 2 weeks.

    4. Received chemotherapy or radiation therapy within 2 weeks of the first dose of epcoritamab.

    5. Concomitant disease requiring permanent or high-dose immunosuppressive therapy.

    6. Received vaccination with live vaccines within 28 days prior to the first dose of epcoritamab.

    7. Clinically significant cardiac disease

    8. Major surgery within 4 weeks

    9. Hepatitis B or C seropositivity (unless clearly due to vaccination)

    10. History of human immunodeficiency virus (HIV)

    11. Unable or unwilling to comply with contraceptive requirements during treatment and for 12 months after last dose of of epcoritamab.

    12. For R/R CLL Cohort - Any history of RS or evidence indicating a potential Richter's transformation.

    13. For RS Cohort - Transformation of CLL to Hodgkin variant of RS

    14. For RS Cohort - Diagnosis of Richter's syndrome not of the DLBCL subtype such as Hodgkin's lymphoma, prolymphocytic leukemia.

    15. For RS Cohort - Subject received autologous HSCT within 3 months prior to the first dose of epcoritamab.

    16. For RS Cohort - Subject received more than 1 prior line of therapy for RS.

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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama Tuscaloosa Alabama United States 35487
    2 David Geffen School of Medicine Los Angeles California United States 90095
    3 Memorial Healthcare System Hollywood Florida United States 33021
    4 Memorial Healthcare System Pembroke Pines Florida United States 33028
    5 University of Michigan Comprehensive Cancer Center Ann Arbor Michigan United States 48190
    6 Henry Ford Medical Group Detroit Michigan United States 48202
    7 Hackensack Meridian Hospital Hackensack New Jersey United States 07601
    8 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    9 The University of Texas Southwestern Medical Centre Dallas Texas United States 75390
    10 Fred Hutchinson Cancer Research Center Seattle Washington United States 98109
    11 AZ Sint-Jan Bruges Belgium 8000
    12 Universitair Ziekenhuis Gent Gent Belgium 9000
    13 UZ Leuven Leuven Belgium 3000
    14 Rigshospitalet København Hovedstaden Denmark 2100
    15 Aalborg University Hospital Aalborg Denmark 9100
    16 Odense University Hospital Odense Denmark 5000
    17 Roskilde Sygehus Roskilde Denmark 4000
    18 Vejle Sygehus Vejle Denmark 7100
    19 Århus University Hospital Århus Denmark 8000
    20 Universitaetsklinikum Schleswig-Holstein- Karl-Lennart-Krebscentrum Kiel Germany 24105
    21 Universitaetsklinikum Koeln Koeln Germany 50937
    22 Amsterdam UMC Amsterdam Netherlands 1105
    23 Universitair Medisch Centrum Groningen Groningen Netherlands 9713

    Sponsors and Collaborators

    • Genmab
    • AbbVie

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Genmab
    ClinicalTrials.gov Identifier:
    NCT04623541
    Other Study ID Numbers:
    • GCT3013-03
    • 2020-000848-57
    First Posted:
    Nov 10, 2020
    Last Update Posted:
    Jun 16, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Genmab
    DuoBody®
    Monoclonal antibodies
    Anti-CD3
    Anti-CD20
    Additional relevant MeSH terms:
    Leukemia
    Leukemia, Lymphoid
    Leukemia, Lymphocytic, Chronic, B-Cell
    Syndrome

    Study Results

    No Results Posted as of Jun 16, 2022