SNK01/Checkpoint Inhibitor Combo Yields Sustained Remission in Advanced SRC Sarcoma Case
The FDA authorized the natural killer cell therapy combo for compassionate use.
The natural killer (NK) cell therapy SNK01 appears to be safe with some evidence of clinical activity when combined with checkpoint inhibitors (CI) in patients with advanced sarcomas, independent of PD-L1 status.
These data, from 8 patients for which the FDA authorized compassionate use of the therapy, were presented at the European Society for Medical Oncology (ESMO) Congress 2022, September 9-13, in Paris, France, by Victoria S. Chua, MD, director, clinical research, Sarcoma Oncology Center.
“For patients with advanced sarcomas in the relapsed/refractory setting, few effective treatment options exist. The likelihood of response or tumor control diminishes with each subsequent line of therapy,” Chua and colleagues wrote. “Monotherapy of PD-L1 inhibitors has shown modest to no activity in sarcomas, especially in tumors with low or no PD-L1 expression. NK cells have been implicated in the antitumor response to immune CI with evidence suggesting a role in PD-L1-negative tumors."
SNK01 is a first-in-kind, autologous, non-genetically modified NK cell therapy. It is designed to have enhanced cytotoxicity and an over 90% activating receptor expression to allow it to be consistently produced from heavily pretreated patients.
READ MORE: TCR T-Cell Therapy Shows Efficacy Across MAGE-A4+ Solid Tumors
The patients had a median age of 58.8 years (range, 16-75), a median of 4.5 lines of prior therapy (range, 3-10), and 5 were male. Sarcomas were all stage 4 and types were chondrosarcoma, small round cell sarcoma (SRCS), leiomyosarcoma, pleomorphic sarcoma, uterine sarcoma, osteosarcoma, mucinous adenocarcinoma, and a sarcoma not otherwise specified (NOS).
All 8 patients received their first immune checkpoint inhibitor (ICI) dose but only 5 were able to receive the ICI and SNK01 combination dose. Patients received 200 mg of pembrolizumab or 240 mg of nivolumab in addition to 2 x 109 cells. No grade 2 or 3 toxicities were reported in any patients that received ICI and SNK01 combination doses.
The best response was seen in the patient with SRCS who, as of August 2022, has remained in remission through 24 months and 36 combination doses of pembrolizumab and SNK01 and has no evidence of disease and no toxicities. This patient had a PDL1-negative tumor and whose disease was refractory to 5 prior lines of therapy. The patient with uterine sarcoma (PD-L1 negative) had a partial response and the patient with chondrosarcoma (10% PD-L1) had a partial response but died from complications from surgery.
The patients with leiomyosarcoma, osteosarcoma, and sarcoma NOS passed away prior to receiving the combination dose while the patients with pleomorphic sarcoma (20% PD-L1) and mucinous adenocarcinoma (25% PD-L1) experienced disease progression. Patients whose disease progressed reported quality of life improvements and became eligible for salvage chemotherapy, resulting in additional clinical response.
“SNK01 combined with CIs appears to be safe and demonstrates clinical activity against several types of heavily pre-treated advanced sarcoma, independent of PD-L1 status. It may also keep rapidly progressing disease stable enough to allow additional cytotoxic chemotherapy. This intriguing combo data warrants further study,” Chua and colleagues wrote.
Click here to read more coverage of ESMO Congress 2022.
