Background: BO-112 is a double stranded synthetic RNA formulated with polyethyleneimine. By mimicking a viral infection, it mobilizes the immune system, including activation of dendritic cells, CD8 T-cell infiltration, induction of interferons, and enhancement of immunogenic cell death. Intratumoral (IT) BO-112 has been tested both alone and in combination with anti-PD-1 therapies in a phase I trial (NCT02828098), which showed an overall response rate (ORR) of 11% and disease control rate (DCR) of 46% in patients with multiple tumor types and a tolerable safety profile. While anti-PD1 therapies have shown promise in select subtypes of soft tissue sarcoma (STS), their overall efficacy in STS has been limited. We hypothesize that BO-112, in combination with radiotherapy (RT), may reverse resistance to anti-PD1 therapy in a subset of patients with STS.

Methods: This is an exploratory phase I study of IT BO-112 in combination with nivolumab in patients with STS planning to undergo neoadjuvant RT (NCT04420975) and surgery. BO-112 at a dose of 1 mg will be administered intratumorally on days 1, 8 and 15; nivolumab 240 mg will be administered intravenously on days 8 and 22. Patients will receive 5 fractions of neoadjuvant RT between day 8 and 12, followed by surgical resection between days 26 and 50. Twenty patients with newly diagnosed high grade histologically confirmed STS of the extremity, trunk or retroperitoneum amenable for IT injection will be included. Allowed histological subtypes are undifferentiated pleomorphic sarcoma, myxofibrosarcoma, leiomyosarcoma, dedifferentiated liposarcoma and synovial sarcoma.The primary objective is to explore the safety of BO-112 in combination with nivolumab in patients undergoing preoperative RT. The study includes stopping rules based on the frequency of dose limiting toxicities. As an exploratory single arm pilot study results will be reported using purely descriptive statistics. Tumor and blood specimens collected at baseline, at each IT BO-112 injection, and surgery will allow evaluation of the dynamic changes in tumor immune infiltration, T cell receptor repertoire, and tumor necrosis. These dynamic changes, along with putative biomarkers, such as baseline tumor mutational load, copy number alterations, tumor immune composition, tumor and immune gene expression signatures, and PD-L1 expression, will be related to individual subject tumor responses. The 2-year rate of local recurrence and distant metastasis will also be assessed. This study began accrual in December 2020 and is open.

Citation Format: Anusha Kalbasi, Fritz C. Eilber, Arun Singh, Bartosz Chmielowski, Nicholas Bernthal, Brooke Crawford, Joseph G. Crompton, Varand Ghazikhanian, Leanne Seeger, Kambiz Motamedi, Michael L. Douek, Carol Felix, Vincent Basehart, Helena Escuin-Ordinas, Marisol Quintero, Sonia Macia. A phase I study of intratumoral BO-112 and nivolumab for resectable soft tissue sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT221.