Abstract CT079: A Phase I study of PNK-007, allogeneic, off the shelf NK cell in relapsed/refractory AML (NCT02781467)
Authors: Cooley Sarah , Hari Parameswaran , McCloskey James , Byrne Michael , Wang Eunice , Hussein Mohamad , Giarritta Erica , Zhang Xiaokui , Hariri Robert , Miller Jeffrey S. 
Published: August 2019

Abstract
Background: PNK-007 is an allogeneic, off the shelf cell therapy enriched for CD56+/CD3- NK cells expanded from placental CD34+ cells. PNK-007 exhibits cytotoxicity against various cancer cell types, including acute myeloid leukemia (AML), and secretes cytokines during co-culture with cancer cells. Reported here are results of a Phase I first-in-man study in relapsed/refractory (r/r) AML patients (pts).
Methods: Placental CD34+ cells were cultivated in the presence of cytokines for 35 days to generate PNK-007 under the cGMP standards with release testing. HLA matching/KIR mismatching were not used. Eligible pts received a single PNK-007 infusion of 1, 3, or 10 million (M) cells/kg followed by rhIL-2 administered subcutaneously at 6M units every other day for up to 6 doses to facilitate PNK-007 expansion. Eligible pts with r/r AML received Lymphodepletion with Cy-Flu (60mg/kg Cy Days -5 to -4; 25mg/m2 Flu Days -6 to -2).
Results: Ten pts, age range 30-70 years (median 66), KPS &gt;70%, and WHO Classifications of recurrent genetic abnormalities (n=4), MDS-related changes (n=4), not otherwise specified (n=2), were treated with a single PNK-007 infusion followed by 5 to 6 rhIL-2 injections. These pts received 1 to 5 (median 3) prior lines of AML therapy and included 5 pts with a history of MDS and 5 pts received prior allogeneic SCT. Flow cytometric analysis of pt blood showed in vivo PNK-007 persistence, proliferation (Ki67) and maturation at dose levels 3M and 10M cells/kg between 7 to 28 days post-infusion. Functional analysis of PNK-007 isolated from 1 pt showed NK cell effector activity. One pt treated with 10M cells/kg PNK-007 developed Cytokine Release Syndrome (CRS) 14 days after infusion and was effectively managed with tocilizumab. This CRS event was deemed a dose-limiting toxicity. The other 9 pts did not experience CRS symptoms and PNK-007 was well tolerated with no infusion reactions or GvHD. No deaths were attributed to PNK-007. Efficacy was defined as complete remission rate (CR or CRp) at Day 42 and overall survival (OS) at 24 months. Although 2 of 8 efficacy evaluable patients had evidence of clinical benefit, Day 42 bone marrow biopsy could not be performed in either pt. On Day 21, a complete response with incomplete platelet recovery (CRp) was observed in the pt who experienced CRS. On Day 14, another patient treated at 10M cells/kg was observed to achieve MLFS. All pts died during the follow-up period of the study; 80% due to progressive AML and 20% due to AML-related complications. Median OS was 2.4 months.
Conclusion: PNK-007 is a fully allogeneic, off the shelf CD34+ derived NK cell product. A single infusion of PNK-007 up to 10M cells/kg with rhIL-2 following Cy-Flu conditioning was safe and well tolerated, with one treatable CRS event observed. Two of 10 pts treated achieved clinical response, assessed by the investigators as CRp and MLFS. Observed clinical data warrant further evaluation of PNK-007 treatment in AML.
Citation Format: Sarah Cooley, Parameswaran Hari, James McCloskey, Michael Byrne, Eunice Wang, Mohamad Hussein, Erica Giarritta, Xiaokui Zhang, Robert Hariri, Jeffrey S. Miller. A Phase I study of PNK-007, allogeneic, off the shelf NK cell in relapsed/refractory AML (NCT02781467) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT079.