Abstract 851: AdAPT-001 demonstrates potent oncolytic activity, high levels of TGFβ inhibition, and encouraging clinical activity in refractory sarcoma: update of the BETA-PRIME trial and preclinical correlates

Soft tissue sarcomas are an exceedingly rare and aggressive malignancy, occurring in about 5000 patients per year with an estimated median overall survival of around 12-18 months. Standard chemotherapy includes doxorubicin alone or with ifosfamide with high toxicity and low response rates. Other approved therapies in sarcoma are trabectedin, eribulin, and pazopanib, but their response rates are less than 10%. Immunotherapy trials have been largely disappointing. In the SARC028 phase 2 clinical trial, the PD-1 inhibitor, pembrolizumab, had limited activity except in undifferentiated pleomorphic sarcoma and liposarcoma. In the Phase 2 Alliance A091401 trial, the response to nivolumab was very low at only 5%, which led the investigators to arrive at a conclusion of medical futility, stating that, “Nivolumab alone does not warrant further study in an unselected sarcoma population given the limited efficacy”. AdAPT-001 is currently under investigation in a Phase 1/2 clinical trial for the treatment of advanced malignant solid tumor(s) for patients who have received all conventional therapies considered appropriate by Investigator. To date, of the 25 patients who received multiple doses of AdAPT-001 plus a checkpoint inhibitor, 14 of them were diagnosed with soft tissue sarcoma. Of these 14 patients, 69.2% (9/14 patients) reached a 3-month PFS and 35.7% (5/14) had an objective response. Most of these sarcomas had previously progressed on a PD-1 or PD-L1 inhibitor or were considered nonimmunogenic and, therefore, unsuitable for checkpoint inhibitor monotherapy. To date, the median PFS is 8.5 months. To further understand the activity of AdAPT-001 in sarcoma, we analyzed the lytic activity, TGFβ trap expression, and checkpoint expression patterns of sarcoma cell lines after infection. We demonstrate robust infection, replication, lysis and high-levels of TGFβ trap expression in sarcoma cell lines and objective responses, including pathologic complete responses, among patients who have progressed on chemotherapy and immunotherapy. Citation Format: Chris Larson, Ana Sanchez, Farah Hedjran, Garett Soapes, Bryan Oronsky, Anthony P. Conley, Meaghan Stirn, Tony Reid. AdAPT-001 demonstrates potent oncolytic activity, high levels of TGFβ inhibition, and encouraging clinical activity in refractory sarcoma: update of the BETA-PRIME trial and preclinical correlates [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 851.