Abstract CT108: A Phase I study of PNK-007, allogeneic, off the shelf NK cell, post autologous transplant in multiple myeloma (NCT02955550)
Authors: Holstein Sarah A. , Cooley Sarah A. , Hari Parameswaran , Jagannath Sundar , Balint Catherine R. , Touw William van der , Donato Michele L. , McCarthy Philip L. , Wallace Paul K. , Zhang Xiaokui , Hariri Robert J. , Hussein Mohamad A. , Vij Ravi 
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 exhibit cytotoxicity against various cancer cell types, including multiple myeloma (MM), and secrete cytokines during co-culture with cancer cells. This is a Phase I study of single infusion PNK-007 after autologous stem cell transplant (ASCT) in MM.
Methods: Placental CD34+ cells were cultivated in the presence of cytokines for 35 days to generate PNK-007 under cGMP standards followed by release testing. HLA matching and KIR mismatching were not used. Four treatment arms were evaluated on eligible patients (pts) following ASCT: 10 million (M) cells/kg Day (D) 14 with or without rhIL-2, 30M cells/kg D14 with rhIL-2 or 30M cells/kg D7 with rhIL-2. rhIL-2 was administered subcutaneously at 6M units every other day for up to 6 doses to facilitate PNK-007 expansion. Pts received variable pre-ASCT induction therapy. Maintenance therapy was permitted after the Day 90-100 visit (D90). Enrollment is complete, and all pts have completed the D90 visit as of the cutoff date Oct 26, 2018.
Results: 15 pts who received PNK-007 (12 of whom received rhIL-2) were evaluated for clinical response at D90. Pts aged 44-69 yrs included 12 newly diagnosed (ND)MM and 3 relapsed/refractory (RR)MM. The 3 RRMM received 1, 2 or 5 prior lines of therapy, with 2 pts having previous ASCT. All pts had been exposed to IMiDs and PIs. No dose-limiting toxicity, GvHD, graft failure or graft rejection were observed. No serious adverse events (AEs) were attributable to PNK-007 and the reported AEs were consistent with AEs related to ASCT. Based on physician assessed responses by International Myeloma Working Group pre-ASCT, 10/15 pts achieved VGPR or better (1 CR and 9 VGPR), and by D90, 12/15 pts achieved VGPR or better (5 CR or sCR and 7 VGPR). Using a validated Euro-flow minimal residual disease (MRD) assay by bone marrow aspirate (BMA), pre-ASCT, 4/15 pts were MRD negative (MRD-), and by D90, 10/15 pts were MRD-. At one-year post-ASCT, 4/6 pts were MRD-, with 1 converting to MRD-, 1 inadequate sample, and 1 remaining MRD+. PNK-007 did not interfere with immune reconstitution kinetics. Administration of rhIL-2 coincided with a transient increase in circulating regulatory T cell levels. Host NK cells reached a maximum level between 21-28 days post-ASCT followed by contraction independent of rhIL-2 administration.
Conclusion: PNK-007 is the first fully allogeneic, off the shelf CD34+ derived NK cell product in MM clinical trials. A single infusion of PNK-007 up to 30M cells/kg with and without rhIL-2 was well tolerated in the post-ASCT setting. We established the feasibility of infusing PNK-007 as early as 7 days post-ASCT without negative impact on blood count recovery. Attainment of BMA MRD- status was observed in 10/15 pts at D90. These clinical data are encouraging and warrant further evaluation.
Citation Format: Sarah A. Holstein, Sarah A. Cooley, Parameswaran Hari, Sundar Jagannath, Catherine R. Balint, William van der Touw, Michele L. Donato, Philip L. McCarthy, Paul K. Wallace, Xiaokui Zhang, Robert J. Hariri, Mohamad A. Hussein, Ravi Vij. A Phase I study of PNK-007, allogeneic, off the shelf NK cell, post autologous transplant in multiple myeloma (NCT02955550) [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 CT108.