Overview
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.
Description
This is a multicenter, nonrandomized, open-label, parallel assignment, dose-escalation, and dose-expansion study to evaluate the safety and tolerability, find an appropriate dose to optimize safety and efficacy, and evaluate clinical activity of azer-cel in participants with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL), non-Hodgkin lymphoma (NHL), and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Before initiating azer-cel, participants will be administered lymphodepletion (LD). At Day 0 of the Treatment Period, participants will receive an intravenous (IV) infusion of azer-cel potentially followed by interleukin-2 (IL-2). All participants will be monitored through D720 or progression. All participants who receive a dose of azer-cel will be asked to consent to a separate long-term follow-up (LTFU) study for up to 15 years after exiting this study.
Eligibility
Key Inclusion Criteria
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.
Key Exclusion Criteria
Criteria for B-ALL:
• Burkitt cell (L3 ALL) or mixed-lineage acute leukemia.
Criteria for NHL:
- Requirement for urgent therapy due to tumor mass effects such as bowel obstruction or blood vessel compression.
- Active hemolytic anemia.
Criteria for B-ALL and NHL:
- No active CNS disease, excluding PCNSL
- History of another primary malignancy
- Any form of primary immunodeficiency (for example, severe combined immunodeficiency disease).
- 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 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.
- History of concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome, or any other known bone marrow failure syndrome.
- Active uncontrolled autoimmune disease requiring active immunosuppression at the time of Screening (excluding participants needing steroids for physiologic replacement).
- Participant has received stem cell transplant within 90 days before Screening.
- Participant has active graft-versus-host disease (GvHD) symptoms.
- 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.
- Presence of pleural/peritoneal/pericardial catheter, as well as permeant biliary and ureteral stents (does not apply to intravenous lines).
- 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.
