A Phase 1/1b, Open-label, Dose-escalation, Dose-expansion, Parallel Assignment Study to Evaluate Safety and Clinical Activity of PBCAR0191 (Azercabtagene Zapreleucel or Azer-cel) in Subjects With Relapsed/Refractory (r/r) Non-Hodgkin Lymphoma (NHL) and r/r B-cell Acute Lymphoblastic Leukemia (B-ALL)
This is a Phase 1/1b, nonrandomized, open-label, parallel assignment, dose-escalation, and dose-expansion study to evaluate the safety and clinical activity of azer-cel, an allogeneic anti-CD19 CAR T, in adults with r/r B ALL, r/r B-cell NHL and CLL/SLL.
⁃ Criteria for B-ALL:
⁃ • Participant has confirmed unequivocal r/r CD19+ B-ALL.
⁃ Criteria for NHL and CLL/SLL:
⁃ • Participant has unequivocal aggressive CD19+ r/r B-cell NHL that is confirmed by tumor biopsy tissue from last relapse after CD19-directed therapy.
⁃ For Phase 1 Dose Escalation:
• Diffuse large B-cell lymphoma (DLBCL) including Richter's transformation
• Follicular lymphoma (FL) including Grade 3 or transformed FL
• High-grade B-cell lymphoma (HGBCL)
• Primary mediastinal lymphoma
⁃ For Phase 1b Dose Expansion (CAR T-relapsed cohort):
• DLBCL not otherwise specified (NOS)
• HGBCL
• DLBCL transformed from the following indolent lymphoma subtypes (FL, Marginal Zone lymphoma \[MZL\], and Waldenstrom's Macroglobulinemia \[WM\])
• Other large B-cell lymphoma (LBCL) subtypes may be enrolled with approval from the Medical Monitor.
• Participants previously treated with CD19-directed autologous CAR T therapies have received no more than 2 lines of therapy after administration of their previous CAR T product.
• For the expansion CAR T-relapsed cohort only: Participants must have received autologous CD19-directed CAR T therapy and demonstrated clinical response to the treatment at Day 28 or later, followed by relapse or progression.
⁃ For Phase 1b dose expansion (CAR T-naive cohort):
• DLBCL NOS
• DLBCL transformed from the following indolent lymphoma subtypes (FL, MZL, and WM)
• HGBCL
• FL (Grade 1-3a)
• MZL that is fluorodeoxyglucose (FDG)-avid on positron emission tomography (PET) scan
• WM
• CLL/SLL
• Primary central nervous system (CNS) lymphoma (PCNSL)
• Other LBCL subtypes may be enrolled with approval from the Medical Monitor.
• Participant must have received at least 1-2 prior lines of therapy, depending on histological subtype but no more than 7 systemic lines of anti-cancer therapy.
⁃ Criteria for both B-ALL, NHL, and CLL/SLL:
• Eastern Cooperative Oncology Group performance status score of 0 or 1.
• An estimated life expectancy of at least 12 weeks according to the investigator's judgment.
• Seronegative for human immunodeficiency virus antibody.
• Participant has adequate bone marrow, renal, hepatic, pulmonary, and cardiac function.