Testing azer-cel, a donor-derived CAR T therapy, in adults with relapsed blood cancers

Trial details

Who runs it

Imugene Limited

Trial code

NCT03666000

Record updated

8 September 2026

Original description

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.Read full original descriptionShow less

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.

Inclusion: 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.

Exclusion: Requirement for urgent therapy due to tumor mass effects such as bowel obstruction or blood vessel compression; History of hepatitis B or hepatitis C currently receiving ongoing antiviral therapy; Any known uncontrolled cardiovascular disease at the time of Screening that, in the investigator's opinion, renders the participant ineligible; History of hypertension crisis or hypertensive encephalopathy within 3 months prior to Screening; History of concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome, or any other known bone marrow failure syndrome; Participant has received stem cell transplant within 90 days before Screening; Participant has received a systemic biologic agent for treatment of the disease under study within 28 days of LD, other systemic anti-cancer therapy within 10 days or 5 half-lives (whichever is shorter) of LD, and no pulse steroid for disease control within 3 days of LD; Radiotherapy within 4 weeks before Screening; Participant has received live vaccine within 4 weeks before Screening. Note: Non-live virus vaccines are not excluded; Participant has received CD19-directed therapy other than autologous CD19-directed CAR T therapy within 90 days of the anticipated start date of LD; Additional criteria apply; No active CNS disease, excluding PCNSL; History of another primary malignancy; Any form of primary immunodeficiency (for example, severe combined immunodeficiency disease); History of severe immediate hypersensitivity reaction to any of the agents used in this study; Presence of a CNS disorder that, in the opinion of the investigator, renders the participant ineligible for treatment; Active uncontrolled autoimmune disease requiring active immunosuppression at the time of Screening (excluding participants needing steroids for physiologic replacement); Participant has active graft-versus-host disease (GvHD) symptoms; Criteria for B-ALL:; Burkitt cell (L3 ALL) or mixed-lineage acute leukemia; Criteria for NHL:; Active hemolytic anemia; Criteria for B-ALL and NHL:; Presence of pleural/peritoneal/pericardial catheter, as well as permeant biliary and ureteral stents (does not apply to intravenous lines).

ClinicalTrials.gov NCT03666000