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

Korábbi kezelés

• Received prior treatment with a CD3×CD20 bispecific antibody.
• Received any prior allogeneic hematopoietic stem cell transplantation (HSCT) or solid organ transplantation.
• Received chimeric antigen receptor (CAR) T-cell therapy within 100 days or an investigational drug within 4 weeks, prior to first dose of trial drug.
• Received vaccination with live vaccines within 28 days.
• Has had major surgery within 4 weeks.
• For R/R CLL - Venetoclax Combination Therapy arm: received venetoclax within 24 months prior to beginning venetoclax ramp-up for this trial or has progressed on venetoclax treatment.
• RS - Lenalidomide Combination Therapy and RS Monotherapy Arms - received more than 2 prior lines of therapy for RS.
• R/R CLL - Pirtobrutinib Combination Therapy Arm - Prior exposure to a non-covalent (reversible) BTK inhibitor or a BTK degrader.
• Pirtobrutinib Combination Therapy Expansion Arms:
  • History of bleeding disorders or participants requiring therapeutic anticoagulation with warfarin or another vitamin K antagonist
  • Require continuous treatment with or have received strong cytochrome P450 (CYP) 3A inhibitors or strong/moderate CYP3A inducers within 4 to 5 half-lives or 14 days prior to the first dose of pirtobrutinib.
  • NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

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• Autoimmune disease or other diseases that require permanent or high-dose immunosuppressive therapy.
• Clinically significant cardiac disease.
• Known current malignancy other than inclusion diagnosis.
• Known history of human immunodeficiency virus (HIV).
• For R/R CLL arms - Any history of RS or evidence indicating a potential Richter's transformation.
• For all RS arms - Diagnosis of Richter's syndrome not of the DLBCL subtype such as Hodgkin's lymphoma, prolymphocytic leukemia.

• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
• Evidence of CD20 positivity in a sample representative of the disease at Screening.
• Acceptable hematology parameters and organ function based on baseline bloodwork.
• Life expectancy >3 months on standard of care (SOC) for CLL, >3 months for RS.
• For R/R CLL arms - Must have active CLL/SLL disease requiring treatment per iwCLL 2018 criteria.
• For R/R CLL monotherapy arms - Received at least 2 prior lines of systemic anti-neoplastic therapy including a Bruton's tyrosine kinase (BTK) inhibitor or at least 1 prior line of systemic antineoplastic therapy, including treatment with (or intolerance of) a covalent BTK inhibitor (cBTKi) and a B-cell lymphoma 2 (BCL-2) inhibitor.
• For all RS arms - Have tumor biopsy-proven CD20+ Diffuse large B-cell Lymphoma (DLBCL) and a clinical history of CLL/SLL.
• 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.
• For all RS arms - Must provide mandatory formalin-fixed, paraffin-embedded (FFPE) tumor biopsy sample.
• For RS - monotherapy arm: Deemed as ineligible for chemoimmunotherapy at investigator's discretion or participant who refuses to receive intensive chemotherapy
• 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
  • A woman must agree not to breastfeed a child during treatment and for at least 28 days after discontinuation from study.
• For RS - R-CHOP combination Therapy Arm -
  • Eligible for treatment with R-CHOP.
  • Females of childbearing potential must use highly effective contraceptive measures while taking R-CHOP and for 12 months after stopping treatment.
  • A woman must agree not to breastfeed a child during treatment or until 12 months after last treatment.
• For R/R CLL - venetoclax combination Therapy arm - after receiving at least 1 prior line of systemic antineoplastic therapy.
  • Presence of measurable disease.
  • Must take prophylaxis for tumor lysis syndrome (TLS).
• For R/R CLL pirtobrutinib combination Therapy arm:
  • Must have active CLL/SLL disease requiring treatment per iwCLL 2018 criteria.
  • Presence of measurable disease.
  • Previous treatment with at least one and a maximum 3 prior lines of therapy including a cBTKi.
  • Diagnosis of CLL/SLL that met published iwCLL criteria.
• Non-US Participants Only - Participants with TN HR CLL - Pirtobrutinib Combination Therapy Expansion:
  • Diagnosis of CLL/SLL that met published iwCLL criteria 2018.
  • Must have active CLL/SLL disease that needs treatment per iwCLL
  • Must take prophylaxis for TLS based on their TLS risk evaluation upon initiation of trial drug.
  • Must have one or more high-risk features.
  • Presence of measurable disease.