Dose-escalation and Dose-expansion Study of Safety of Azer-cel (PBCAR0191) in Participants With Relapsed/Refractory (r/r) Non-Hodgkin Lymphoma (NHL) and r/r B-cell Acute Lymphoblastic Leukemia (B-ALL)

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 and Con-BTKi cohort):

For indication with an approved autologous CAR T-cell therapy, participants must be ineligible for or unable to access autologous CAR T-cell therapy.

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.

Participants enrolling into the Con-BTKi cohort must:

Be receiving a BTKi (as a monotherapy or combination therapy) as the last, systemic anti-cancer regimen before study entry. Alternatively, if previously refractory to one or more BTK inhibitor(s) and the last systemic anti-cancer therapy before study entry did not include a BTKi, one of the previous BTK inhibitors may be used.

Have radiologic or clinical disease progression while on the BTKi

Agree to remain on BTKi therapy during the protocol-defined BTKi treatment window

Have been tolerant to BTKi 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.

What this study is about