A phase 1 trial evaluated the combination in patients regardless of PD-L1 status and no differences were seen between those negative or positive.
SNK01, a natural killer (NK) cell therapy, in combination with avelumab, was well-tolerated in patients with advanced refractory sarcoma with some evidence of clinical response, according to an interim analysis of a phase 1 study (NCT03941262).
Data from the interim analysis were presented at the 2022 American Society of Clinical Oncology (ASCO) meeting, held June 3-7, 2022, in Chicago, Illinoisby Sant P. Chawla, MD, FRACP, director, Sarcoma Oncology Center, professor, University of California Los Angeles, and oncologist, Cedars Sinai Comprehensive Cancer Center.
“For patients 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... 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,” Chawla and colleagues wrote.
SNK01 is an autologous, first-in-kind, nongenetically modified NK cell therapy with highly enhanced cytotoxicity. It can be consistently produced from heavily pretreated patients and has over 90% activating receptor expression. Avelumab is an anti-PD-L1 immunotherapy that engages both the adaptive and innate immune systems. The combination was hypothesized to have efficacy in overcoming the immunosuppressive tumor microenvironment.
The phase 1 study is primarily evaluating safety via incidence and severity of adverse events. Secondary endpoints include overall response rate (ORR), progression free survival (PFS), and overall survival. Patients were eligible regardless of PD-L1 status and treatment was permitted to continue indefinitely until unacceptable toxicityor disease progression.
The phase 1 study consists of 4 cohorts of up to 18 patients treated with 800 mg of avelumab and 4 x 109 SNK01 cells every 2 weeks via intravenous infusion. Fifteen patients, 8 male and 7 female with a median age of 50 years (range, 20-75) have been enrolled as of February 1, 2022. Patients had a median 5 lines of prior therapy (range, 1-8) and sarcoma subtypes included leiomyosarcoma (n = 6), osteosarcoma (n = 2), pleomorphic liposarcoma (n = 1), Ewing’s sarcoma (n = 1), epithelioid sarcoma (n = 1), epithelioid mesothelioma (n = 1), endometrial stromal sarcoma (n = 1), and sarcoma NOS (n = 1).
Investigators found that participants experienced grade 2/3 AEs related to avelumab but not SNK01. Some evidence of clinical activity was seen, with a best objective response by RECIST 1.1 criteria of partial response in 2 patients and ORR of 13.3%. Three patients had stable disease and median PFS was 11.14 weeks. Response seems independent of PD-L1 status. While many patients progressed during treatment, several still reported improvements in quality of life. This allowed some patients to become eligible to be treated with additional salvage chemotherapy, which resulted in some additional clinical response.
“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,” Chawla and colleagues concluded.