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

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ClinicalTrials.gov Identifier: NCT04623541
Recruitment Status : Recruiting
First Posted : November 10, 2020
Last Update Posted : March 18, 2022
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
Genmab

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
Relapsed/Refractory Chronic Lymphocytic Leukemia Richter's Syndrome 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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : November 30, 2020
Estimated Primary Completion Date : August 2024
Estimated Study Completion Date : August 2026


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 Name: 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 Name: GEN3013; DuoBody®-CD3xCD20




Primary Outcome Measures :
  1. Dose escalation phase: Incidence of dose limiting toxicities (DLTs) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: From first dose until the end of the treatment period, expected average of 1 year ]
    Evaluate the immunogenicity of epcoritamab



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04623541


Contacts
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Contact: Genmab Trial Information +4570202728 clinicaltrials@genmab.com

Locations
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Sponsors and Collaborators
Genmab
AbbVie
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Responsible Party: Genmab
ClinicalTrials.gov Identifier: NCT04623541    
Other Study ID Numbers: GCT3013-03
2020-000848-57 ( EudraCT Number )
First Posted: November 10, 2020    Key Record Dates
Last Update Posted: March 18, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Syndrome
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell