Phase 1/1b Safety Study of Prgn-3006 Ultracar-T in Patients with Relapsed or Refractory CD33-Positive Acute Myeloid Leukemia and Higher Risk Myelodysplastic Syndromes
As of July 15, 2022 data cut-off, 24 pts have been treated in C1 (n=10) and C2 (n=14). The study enrolled 20 r/r AML, 1 CMML, and 3 MDS pts with a median age of 60.5 years (33-77). Pts were heavily pre-treated with a median of 3 prior regimens (range, 1-9) and 62.5% of pts (n=15) had prior allogeneic hematopoietic cell transplantation (alloHCT). Pts treated in C1 and C2 received 1.8 to 50 x 106 and 4.4 to 83 x 106 UltraCAR-T cells via intravenous (IV) infusion respectively.
PRGN-3006 infusion at up to 1x106 cells/kg was well tolerated with similar safety profile for pts treated in C1 and C2. There have been no deaths, dose-limiting toxicities (DLTs), or unexpected on-target/off-target toxicities related to PRGN-3006, and no use of the kill switch as of data cut-off. There have been no cases of bone marrow aplasia. Grade 1 cytokine release syndrome (CRS) occurred in 3/10 pts in C1 ((DL1 (n=1), and DL3 (n=2)), and 7/14 pts in C2 ((DL1 (n=1), DL2 (n=2) and DL3 (n=4)). Grade 2 CRS occurred in 3/10 pts in C1 ((DL1 (n=1), and DL3 (n=2)) and 3/14 pts in C2 (DL3 (n=3)). Only 1 pt (DL1, C1) had transient grade 3 CRS that resolved in < 24 hours with tocilizumab and dexamethasone. Plasma levels of IL-15 did not increase with treatment confirming mbIL15 is not shed.
A dose dependent expansion of PRGN-3006 was observed in peripheral blood and bone marrow in both C1 and C2 patients with durable in vivo persistence of UltraCAR-T in the blood for up to 7 months post infusion. Peak expansion in the blood was significantly higher (> 1 log10) in pts treated in C2 with lymphodepletion compared to C1 without lymphodepletion at the same dose level, with the highest peak expansion observed in subjects treated in Cohort 2 at DL3. UltraCAR-T cells expanded in the bone marrow of pts treated in C1 and C2 with the highest peak bone marrow expansion in pts treated in C2 at DL3.
Bone marrow blasts were reduced following treatment in 7/14 (50%) of lymphodepleted pts (C2), with 4 pts experiencing a decrease to ≤5%. AML pts in Cohort 2 (n=10) demonstrated a 30% objective response rate: 1 CRi was bridged to alloHCT and remains in a measurable residual disease negative CR 18 months post-transplant; 1 CRh with complete cytogenetic remission and NGS clearance; and 1 PR in a pt with isolated extramedullary leukemia. No objective responses were observed in CMML (n=1) or MDS (n=3) pts treated to date on the study. In non-lymphodepleted pts (C1), 1/10 pts had durable stable disease lasting > 7 months with persistence of UltraCAR-T cells.