Safety & Efficacy Study of Epcoritamab in Subjects With R/R Chronic Lymphocytic Leukemia and Richter’s Syndrome

Brief Title

Safety & Efficacy Study of Epcoritamab in Subjects With R/R Chronic Lymphocytic Leukemia and Richter's Syndrome

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

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).
    

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 Phase

Phase 1/Phase 2

Study Type

Interventional

Primary Outcome

Dose escalation phase: Incidence of dose limiting toxicities (DLTs)

Secondary Outcome

 Dose expansion phase: Incidence of AEs

Condition

Relapsed/Refractory Chronic Lymphocytic Leukemia

Intervention

Epcoritamab

Study Arms / Comparison Groups

 Epcoritamab in R/R CLL

Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Biological

Estimated Enrollment

102

Start Date

November 30, 2020

Completion Date

August 2026

Primary Completion Date

August 2024

Eligibility 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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

, +4570202728, [email protected]

Location Countries

Belgium

Location Countries

Belgium

NCT ID

NCT04623541

Organization ID

GCT3013-03

Secondary IDs

2020-000848-57

Responsible Party

Sponsor

Study Sponsor

Genmab

Collaborators

 AbbVie

Study Sponsor

, , 

Verification Date

June 2022