Study of Lenzilumab and Axicabtagene Ciloleucel in Participants With Relapsed or Refractory Large B-Cell Lymphoma

A Phase 1/2 Open-label, Multicenter Study of Lenzilumab and Axicabtagene Ciloleucel in Subjects With Relapsed or Refractory Large B-cell Lymphoma (ZUMA-19)

The primary objectives of this study are:

Phase 1: To evaluate the safety of sequenced therapy with lenzilumab and axicabtagene ciloleucel in participants with relapsed or refractory large B-cell lymphoma and identify the most appropriate dose of lenzilumab for Phase 2.

Phase 2: To evaluate the incidence of neurologic events with sequenced therapy given at the recommended Phase 2 dose (RP2D) of lenzilumab in participants with relapsed or refractory large B-cell lymphoma.

This study was intended to be a Phase 1/2, but the planned Phase 2 part has been canceled.

All participants who received an infusion of lenzilumab and axicabtagene ciloleucel will be provided the opportunity to transition to a separate long-term follow-up (LTFU) study, KT-US-982-5968.

Key Inclusion Criteria:

• Individuals with large B-cell lymphoma, including Diffuse large B-cell lymphoma (DLBCL) not otherwise specified, Primary mediastinal large B-cell lymphoma (PMBCL), High-grade B-cell lymphoma (HGBL), and DLBCL arising from Follicular lymphoma (FL)

• Individuals must have relapsed disease after 2 or more lines of systemic therapy, or chemorefractory disease defined as the following:

  • No response to first-line therapy, including the following:

    • Progressive disease (PD) as best response to first therapy
    • Stable disease (SD) as best response after ≥ 4 cycles of first-line therapy (eg, 4 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP)), with SD duration no longer than 6 months from the last dose of therapy

  • No response to ≥ 2 lines of therapy, including the following:

    • PD as best response to most recent therapy
    • SD as best response after ≥ 2 cycles of last line of therapy

• Individuals must have received adequate prior therapy including at a minimum:

  • Anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20 negative, and
  • An anthracycline-containing chemotherapy regimen

• At least 1 measurable lesion according to the International Working Group Lugano Classification. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.

• Magnetic resonance imaging of the brain showing no evidence of central nervous system (CNS) lymphoma

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Individuals with a known medical history of tuberculosis or a risk for tuberculosis exposure require negative tuberculosis testing by either tuberculin skin test or interferon gamma release assay.

• Adequate bone marrow function as evidenced by:

  • Absolute neutrophil count ≥ 1000/μL
  • Platelets ≥ 75,000/μL
  • Absolute lymphocyte count ≥ 100/μL

• Adequate renal, hepatic, cardiac, and pulmonary function as evidenced by:

  • Creatinine clearance (Cockcroft-Gault) ≥ 60 mL/min
  • Serum alanine aminotransferase or aspartate aminotransferase ≤ 2.5 upper limit of normal
  • Total bilirubin ≤ 1.5 mg/dL, except in individuals with Gilbert's Syndrome
  • Cardiac ejection fraction ≥ 50% with no evidence of clinically significant pericardial effusion as determined by echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings
  • No clinically significant pleural effusion
  • Baseline oxygen saturation > 92% on room air

Key Exclusion Criteria:

• History of Richter's transformation of chronic lymphocytic leukemia
• Autologous stem cell transplant (SCT) within 6 weeks of planned axicabtagene ciloleucel infusion
• History of allogeneic stem cell transplantation
• Prior CD19 targeted therapy or prior CAR T cell therapy
• History of pulmonary alveolar proteinosis (PAP)
• History of severe, immediate hypersensitivity reaction attributed to aminoglycosides
• Known history of human immunodeficiency virus (HIV) infection, hepatitis B (HBsAg positive) or hepatitis C (HCV) (anti-HCV positive) infection. A history of hepatitis B or hepatitis C infection is permitted if the viral load is undetectable per quantitative polymerase chain reaction (PCR) and/or nucleic acid testing.
• Individuals with detectable Cerebrospinal fluid (CSF) malignant cells, or brain metastases, or with a history of CNS lymphoma, CSF malignant cells or brain metastases
• History or presence of CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement

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