(P 138) SUSTAINED REMISSION/DISEASE CONTROL USING AUTOLOGOUS ENHANCED NATURAL KILLER CELLS PLUS AN IMMUNE CHECKPOINT INHIBITOR AS TREATMENT FOR RARE CHEMOTHERAPY-RESISTANT ADVANCED SOFT TISSUE SARCOMAS

Objective: To report three unique cases of chemotherapy-resistant advanced soft tissue sarcoma who achieved durable complete and partial responses and durable disease control with autologous enhanced natural killer cells plus an immune checkpoint inhibitor.

Methods: Three patients with rare chemotherapy-resistant soft tissue sarcoma participated in FDA authorized and WIRB approved protocols, received autologous enhanced NK cells (SNK01) 2-4 x 10e9 cells i.v. q 2 weeks and pembrolizumab 200 mg or avelumab 800 mg i.v. q 2 weeks. The histologic subtypes include desmoplastic small round cell tumor (DSRCT), radiation-induced sarcoma (RIS) and undifferentiated spindle cell sarcoma.

Results: Case #1(DSCRT): The tumors gradually decreased in size over one year to a 25.6% response. Patient then underwent a surgical debulking procedure followed by whole abdominal radiation and intraperitoneal chemotherapy, after which he resumed SNK01 and pembrolizumab regimen. His last scan showed sustained complete remission (Figure). He has now received 32 cycles of SNK01 + pembrolizumab over 28 months. The patient is back to work full time and feels great. Case#2 (RIS): Patient had a 38% partial response after four months of treatment, underwent debulking surgery but died of post-surgical infection. The patient had received 18 cycles of SNK01 + pembrolizumab and survived 12 additional months. Case #3 (Undifferentiated spindle cell sarcoma): Patient had durable disease control (stable disease) during the 12-month treatment period. There were no treatment-related Grade 3 or greater adverse events.

Conclusion: These unique case studies clearly demonstrate the potential of SNK01 in controlling tumor growth in conjunction with an ICI. An interesting concept is that improved efficacy may be achieved by combining SNK01, an ICI, and a targeted cell cycle checkpoint inhibitor, e.g., DeltaRex-G, that (1) uniquely targets tumors by binding to abnormal signature proteins and augmenting drug concentration in the TME, and (2) kills not only cancer cells but also proliferative neovasculature, tumor associated growth promoting macrophages, and TAFs that make the stroma which is responsible for downregulating ligands of NK cell activating receptors. Killing TAFs and reducing tumor stroma production with DeltaRex-G would enhance NK cells entry in the TME and favor NK cell-ligand interactions for improved tumor control. Thus, reducing or eliminating tumor stroma with DeltaRex-G could enhance the anti-tumor activity of SNK01 plus ICIs in sarcomas and other solid malignancies.