Preliminary analysis of a phase I study of SNK01 (Autologous Non-genetically Modified Natural Killer Cells With Enhanced Cytotoxicity) monotherapy in patients with advanced solid tumors.

2644 Background: Natural killer (NK) cells play a key role as the main effector cells toward cancer in innate immunity. Thus, a leading approach is to boost NK-cell mediated anti-tumor activity using adoptive transfer of ex vivo activated NK cells. NK cells have always been challenging to grow ex vivo especially when derived from heavily pretreated donors, thus most have focused on universal allogenic donor derived products. SNK01 is a first-in-kind, autologous non-genetically modified NK cell product with significant anti-tumor cytotoxicity and over 90% expression of CD16, NKG2D, NKp46, and DNAM-1, that can be consistently produced even from heavily pre-treated cancer patients (pts). While most if not all NK cell therapy has focused on liquid malignancies, SNK01 has been found to have strong activity against both liquid and solid tumors preclinically. We hypothesized that SNK01 would be safe without need for lymphodepletion and may demonstrate activity against heavily pre-treated solid tumors. Methods: In this Phase 1 dose escalation study (NCT03941262), SNK01 was administered intravenously (IV) weekly for 5 consecutive weeks using a 3+3 design in pts with advanced solid tumors. The starting dose was 1 x 109SNK01 cells and the highest dose was 4 x 109 SNK01 cells. Primary endpoint was safety based on AEs, vitals, laboratory tests, and PEs. Individual NK cell expansion was characterized for increases in cytotoxicity and changes in activating receptor expression. Results: As of Feb 1, 2022, 10 pts with advanced refractory solid tumors have been enrolled. Median age is 50 (range 32 – 75) and 6 were male. Pts had a median 5.5 lines of prior therapy (range 2-10). The subtypes were 4 leiomyosarcoma, 1 chondrosarcoma, 1 NSCLC, 1 small round cell tumor, 1 colorectal, 1 synovial cell sarcoma, 1 angiosarcoma. NK cells were successfully activated and expanded, even from heavily pre-treated pts. Average cytotoxicity was increased over 400% and average activating receptor expression was greater than 90%. There were only two Grade 1 adverse events reported in the 50 total doses given. Best objective response of SD was demonstrated in 7 pts. Of patients who progressed in the dose escalation cohorts, several reported an overall improvement in their QOL. Based on this improvement, patients then became eligible to be treated with additional salvage chemotherapy to which some then showed additional response. Conclusions: SNK01 with high cytotoxicity and activating receptor expression can be consistently produced from heavily pretreated patients. SNK01 was very safe and appears to have some clinical activity against heavily pretreated solid tumors and may even sensitize tumors to additional chemotherapy. SNK01 will be studied further as monotherapy and in various combination regimens. Clinical trial information: NCT03941262.