Initial results from a first in human dose escalation trial of a novel immune stimulating oncolytic adenovirus, AdAPT-001^{TGF-ß Trap}.

2550 Background: As a class, oncolytic adenoviruses (OAV), modified agents of the common cold, specifically target and lyse tumor cells, and by expression of cytotoxic transgenes activate an immune response. AdAPT-001 is an OAV, which carries a transforming growth factor beta (TGF-ß) trap that neutralizes the immunosuppressive and profibrotic cytokine, TGF-ß. Preclinically, AdAPT-001 TGF-ß Trap eradicates non-T-cell infiltrated tumors. The aim of this Phase 1 study was to assess the safety and tolerability and, secondarily, the efficacy of AdAPT-001 TGF-ß Trap after single intra-tumoral injection (IT) (Phase 1a) and multidose IT injection (Phase 1b) in patients with advanced refractory solid tumors. Methods: This was an open label, single-arm, multicenter dose escalation design trial. AdAPT-001 TGF-ß Trap was administered by intratumoral injection. 9 patients were in a single-dose group, where doses of 2.5 x 10 11 , 5.0 x 10 11 , 1.0 x 10 12 viral particles (VPs), were tested, and 19 patients with a median age of 70, 5 median prior regimens, and a median ECOG score of 1 received AdAPT-001 every 2 weeks at 1.0 x 10 12 VPs until progression. Results: AdAPT-001 TGF-ß Trap was well tolerated with local inflammation, fever, and fatigue as the main side effects. No dose limiting toxicities, no grade 4 toxicities, or treatment-related serious adverse events (SAEs) were seen. Tumor types were sarcoma (n = 8), melanoma (n = 2), head & neck (n = 5), gastric (n = 1), rectal (n = 1), breast (n = 1), fallopian (n = 1). Biological activity (virus replication, local reactions, and tumor shrinkage) was observed. The duration of local reactions and virus replication suggested that dosing every 2 weeks was appropriate. The overall responses to treatment were as follows: 5 patients had durable stable disease for 6 months or more, 1 patient had a partial response, and 2 patients demonstrated pseudoprogression with inflammation of uninjected as well as the injected tumor, 5 patients had stable disease for approximately 2 months and 15 patients had progressive disease. 2 abscopal responses have been seen to date. The data also suggest a dose-response relationship, with higher and more frequent doses associated with better outcomes. Peripheral lymphocyte subset analysis and serum cytokine analysis are ongoing. Conclusions: AdAPT-001 TGF-ß Trap is well tolerated and no dose limiting toxicities were observed with the single or multidosing protocol described. Evidence of an antitumor effect was seen. The recommended Phase 2 dose was 1.0 x 10 12 VPs administered by intratumoral injection once every 2 weeks. Combination of AdAPT-001 TGF-ß Trap with a checkpoint inhibitor is planned. Clinical trial information: NCT04673942 .