Interim analysis of a phase I study of SNK01 (Autologous Nongenetically Modified Natural Killer Cells with Enhanced Cytotoxicity) and avelumab in advanced refractory sarcoma.

11517 Background: For patients (pts) with advanced sarcomas in the relapsed/refractory setting, there are very few if any effective salvage treatment options. The likelihood of response and/or tumor control only diminishes with each subsequent line of therapy. Monotherapy of PD-L1 inhibitors has shown modest to no activity in most sarcomas, especially in tumors that have little to no PD-L1 expression. Natural killer (NK) cells have recently been implicated in the antitumor response to immune checkpoint inhibitors with some evidence suggesting a role in PD-L1 negative tumors. SNK01 is a first-in-kind, autologous nongenetically modified NK cell therapy with highly enhanced cytotoxicity and over 90% activating receptor expression which can be consistently produced from heavily pretreated pts. Avelumab is an anti-PD-L1 immunotherapy with dual engagement of both the adaptive and innate immune systems. We hypothesized that this combination would be safe, and together better overcome the immunosuppressive tumor microenvironment. Methods: In this Phase I study (NCT03941262), cohort 4 is comprised of up to 18 pts treated with 800 mg of avelumab + 4 x 109 SNK01 cells every two weeks via IV Infusion. Pts were eligible regardless of PD-L1 status and permitted to continue treatment indefinitely until progression or unacceptable toxicity. The primary endpoint is safety. The secondary endpoints include overall response rate (ORR), progression free survival (PFS), and overall survival (OS). Results: As of February 1, 2022, 15 pts with advanced refractory sarcoma have been enrolled. Median age is 50 (range 20-75) and 8 were male. Pts had a median of 5 lines of prior therapy (range 1-8). The subtypes included 6 leiomyosarcoma, 2 osteosarcoma, 1 pleomorphic liposarcoma, 1 Ewing’s sarcoma, 1 epithelioid sarcoma, 1 epithelioid mesothelioma, 1 endometrial stromal sarcoma, and 1 sarcoma NOS. There were three Grade 2 or 3 adverse events related to avelumab, but unrelated to SNK01. Best objective response by RECIST 1.1 was PR in 2 pts (ORR of 13.3%) and SD in 3 pts. Median PFS is 11.14 weeks. Several pts had PD-L1 negative disease and response appears to be independent of PD-L1 status. Of pts who progressed in this cohort, several reported an overall improvement in their QoL and some pts became eligible to be treated with additional salvage chemotherapy, resulting in some additional clinical response. Conclusions: SNK01 combined with avelumab was safe and well tolerated and appears to have some clinical activity against several types of heavily pretreated advanced sarcoma, independent of PD-L1 status. It may also keep rapidly progressing disease stable enough to allow additional cytotoxic chemotherapy. A proposed study expansion is planned. Clinical trial information: NCT03941262.