Clinical Trials /

Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia

NCT04623541

Description:

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

Related Conditions:
  • Chronic Lymphocytic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia
  • 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

Clinical Trial IDs

  • ORG STUDY ID: GCT3013-03
  • NCT ID: NCT04623541

Conditions

  • Relapsed/Refractory Chronic Lymphocytic Leukemia

Interventions

DrugSynonymsArms
EpcoritamabGEN3013; DuoBody®-CD3xCD20Experimental

Purpose

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

Detailed Description

      The purpose of the escalation part of the trial is to determine the recommended phase 2 dose
      (RP2D) and the maximum tolerated dose (if reached) as well as establish the safety profile of
      epcoritamab in patients with R/R CLL.

      In the expansion part additional patients will be treated with epcoritamab at the RP2D and
      the the purpose is to assess and evaluate the preliminary efficacy, safety and tolerability
      profiles of epcoritamab at the RP2D.
    

Trial Arms

NameTypeDescriptionInterventions
ExperimentalExperimentalExperimental: Epcoritmab Open label single arm
  • Epcoritamab

Eligibility Criteria

        Inclusion Criteria

          1. Subject must sign an ICF, prior to any screening procedures.

          2. Must have active CLL disease that needs treatment per iwCLL2018

          3. R/R CLL after receiving at least 2 prior lines of systemic antineoplastic therapy,
             including treatment with (or intolerance of) a BTK inhibitor

          4. Has Measurable Disease with ≥5 × 109/L (5,000/μL) B lymphocytes in peripheral blood or
             Presence of measurable lymphadenopathy and/or organomegaly

          5. ECOG performance status score of 0 or 1

          6. Screening flow cytometry evidence of CD20 positivity

          7. Has laboratory parameters as follows:

             a. HBG-≥9.0 g/dL; ANC-≥1.0 x 109/L; Platelets-≥30 x 109/L

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

          9. Availability of fresh bone marrow material

         10. Must take prophylaxis for TLS

         11. A woman must be either not of childbearing potential or of childbearing potential and
             practicing a highly effective method of birth control, and must have a negative serum
             beta-human chorionic gonadotropin (beta-hCG) and urine pregnancy test at screening.

         12. 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.

        Exclusion Criteria

          1. Transformation of CLL to aggressive non-Hodgkin lymphoma

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

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

          4. 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 or medical device within 4 weeks, before the first dose.

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

          6. Has autoimmune disease or other diseases that require permanent or high-dose
             immunosuppressive therapy.

          7. Has uncontrolled intercurrent illness.

          8. Toxicities from previous anti-cancer therapies have not resolved to baseline levels or
             to Grade 1 or less except for alopecia and peripheral neuropathy.

          9. Primary central nervous system (CNS) lymphoma or known CNS involvement at screening.

         10. Known past or current malignancy other than inclusion diagnosis

         11. Subject has suspected allergies, hypersensitivity, or intolerance to epcoritamab or
             its excipients.

         12. Subject is unable to tolerate uric acid reducing medications

         13. Has had major surgery within 3 weeks before screening or will not have fully recovered
             from surgery, or has major surgery planned during the time the subject is expected to
             participate in the trial (or within 4 weeks after the last dose of epcoritamab).Known
             history/positive serology for hepatitis B.

         14. Known medical history or ongoing hepatitis C infection that has not been cured.

         15. HIV tested positive at screening.

         16. Is a woman who is pregnant or breast-feeding, or who is planning to become pregnant
             while enrolled in this trial or within 12 months after the last dose of epicoritamab.

         17. Is a man who plans to father a child while enrolled in this trial or within 12 months
             after the last dose of epicoritamab.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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).
Safety Issue:
Description:To identify the recommended phase II dose (RP2D)

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:Pharmacokinetic (PK) parameters Clearance (Cl)
Measure: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
Safety Issue:
Description:PK parameters Volume of Distrubution (Vd)
Measure: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
Safety Issue:
Description:PK parameters maximum (peak) plasma drug concentration (Cmax)
Measure: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
Safety Issue:
Description:PK parameters time to reach maximum (peak) plasma concentration (Tmax)
Measure: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
Safety Issue:
Description:PK parameters Area under the concentration-time curve (AUC) from time zero to last quantifiable sample
Measure: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
Safety Issue:
Description:PK parameters Area under the concentration-time curve (AUC) from time zero to infinity
Measure: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
Safety Issue:
Description:PK parameters pre-dose (trough) concentrations
Measure: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
Safety Issue:
Description:PK parameters elimination half-life (T1/2)
Measure: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
Safety Issue:
Description:pharmacodynamic (PD) marker cytokines
Measure: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
Safety Issue:
Description:pharmacodynamic (PD) marker immune subset CD4
Measure: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
Safety Issue:
Description:pharmacodynamic (PD) marker immune subset CD8
Measure: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
Safety Issue:
Description:pharmacodynamic (PD) marker immune subset B cells
Measure: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
Safety Issue:
Description:pharmacodynamic (PD) marker immune subset activation marker positive/expression level
Measure: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
Safety Issue:
Description:incidence of antidrug-antibodies to epcoritamab
Measure: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)
Safety Issue:
Description:overall response rate
Measure: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)
Safety Issue:
Description:duration of response
Measure: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)
Safety Issue:
Description:time to response
Measure: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)
Safety Issue:
Description:progression free survival
Measure: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)
Safety Issue:
Description:overall survival

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Genmab

Last Updated

November 5, 2020