PRGN-3006

P1, N=88, Active, not recruiting, Precigen, Inc | Recruiting --> Active, not recruiting

P1, N=88, Recruiting, Precigen, Inc | Trial completion date: Jan 2024 --> Aug 2025 | Trial primary completion date: Jan 2023 --> Aug 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.

P1, N=88, Recruiting, PGEN Therapeutics, Inc., a subsidiary of Precigen, Inc. | N=56 --> 88 | Trial completion date: May 2025 --> Jan 2024 | Trial primary completion date: May 2022 --> Jan 2023

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.

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.