PRGN-3005

P1, N=71, Active, not recruiting, Precigen, Inc | Recruiting --> Active, not recruiting

P1, N=71, Recruiting, Precigen, Inc | Trial primary completion date: Dec 2023 --> Dec 2024

Pts received PRGN-3006 infusion without (Cohort 1, C1) or with lymphodepletion (fludarabine 30mg/m2 and cyclophosphamide 500mg/m2 days -5 to -3; Cohort 2, C2)...Only 1 pt (DL1, C1) had transient grade 3 CRS that resolved in < 24 hours with tocilizumab and dexamethasone... Administration of PRGN-3006 UltraCAR-T cells targeting CD33, without or with lymphodepletion, have been well tolerated with low grade CRS. PRGN-3006 UltraCAR-T expressing mbIL15 demonstrated a dose-dependent robust expansion and durable persistence in blood and bone marrow with or without lymphodepletion. Encouraging objective responses have been observed in AML patients treated with lymphodepletion.

Study subjects undergo leukapheresis followed by lymphodepletion with either fludarabine 30mg/m2 and cyclophosphamide 500mg/m2 for 3 days (Arm 1) or 60 mg/kg cyclophosphamide for 2 days (Arm 2). All subjects will be followed for adverse events, CAR-T-related toxicities, disease response and PRGN-3007 cell expansion and persistence. In addition, the mechanisms of safety and effectiveness of PRGN-3007 cells will be evaluated with correlative assays of specific immune response pathways.

Data shown is from 8 mice/group at the start of the study. * p<0.05, ***p<0.001; log rank test.

Ps receive PRGN-3006 infusion without (Cohort 1) or with lymphodepletion (fludarabine 30mg/m 2 and cyclophosphamide 500mg/m 2 days -5 to -3; Cohort 2)...Pts were heavily pre-treated with a median of 3 prior regimens (1-7), with 93% and 80% of pts being r/r to a HMA + venetoclax or intensive chemotherapy, respectively...Cytokine release syndrome (CRS) occurred in 47% of pts (n=7; G1 in 5 pts) with only 1 transient grade 3 event (DL 1, Cohort 1) that resolved in < 24 hours with tocilizumab and dexamethasone...In the setting of mbIL15, there has been a dose-dependent robust expansion and durable persistence of PRGN-3006 with encouraging responses (50%) in patients treated following lymphodepletion. Enrollment is ongoing to DL4, and updated safety, efficacy, PK/PD and cytokine data to be presented.

P1, N=71, Recruiting, PGEN Therapeutics, Inc., a subsidiary of Precigen, Inc. | Trial completion date: Apr 2026 --> Nov 2028 | Trial primary completion date: Apr 2022 --> Dec 2023

Superior efficacy of UltraCAR-T cells was demonstrated in an aggressive murine xenograft model of AML where a single administration of PRGN-3006, only one day after gene transfer, showed significantly higher expansion and persistence; effectively eliminated tumor burden; and significantly improved overall survival compared to traditional CD33 CAR-T cells lacking mbIL15 expression (Blood (2019) 134(S1): 2660)...Key inclusion criteria include an absolute lymphocyte count ≥ 0.2k/µL, KPS > 60%, absence of other active malignancy within 1 year of study entry, daily corticosteroid dose < 10mg of prednisone daily, adequate organ function and a backup allogeneic donor should bone marrow aplasia occur. Hydroxyurea is allowed for cytoreduction with cessation 3 days prior to apheresis/infusion but can be reinitiated post-infusion. To test the hypothesis that expression of mbIL15 on PRGN-3006 cells is sufficient to promote CAR-T cell expansion and persistence, study subjects will receive PRGN-3006 infusion either without prior lymphodepletion (Cohort 1) or following lymphodepleting chemotherapy (Cohort 2 with fludarabine 30mg/m2 and cyclophosphamide 500mg/m2 days -5 to -3)...Currently, the study is in the dose escalation phase and has cleared the lower dose level while demonstrating successful manufacturing of UltraCAR-T cells. Additionally, multi-center expansion of the trial is in progress.

P1, N=71, Suspended, Fred Hutchinson Cancer Research Center | Recruiting --> Suspended

P1, N=71, Recruiting, Fred Hutchinson Cancer Research Center | N=41 --> 71

P1, N=41, Recruiting, Fred Hutchinson Cancer Research Center | Suspended --> Recruiting

P1, N=41, Suspended, Fred Hutchinson Cancer Research Center | Recruiting --> Suspended