BETA prime: a first-in-man phase 1 study of AdAPT-001, an armed oncolytic adenovirus for solid tumors

• Published in: Cancer gene therapy 2024-04, Vol.31 (4), p.517-526
• Main Authors: Conley, Anthony P., Roland, Christina L., Bessudo, Alberto, Gastman, Brian R., Villaflor, Victoria M., Larson, Christopher, Reid, Tony R., Caroen, Scott, Oronsky, Bryan, Stirn, Meaghan, Williams, Jeannie, Burbano, Erica, Coyle, Angelique, Barve, Minal A., Wagle, Naveed, Abrouk, Nacer, Kesari, Santosh
• Format: Article
• Language: English
• Subjects: 631/67/1798; 692/308/153; Adenoviridae - genetics; Adenoviridae Infections; Adenoviruses; Biomedical and Life Sciences; Biomedicine; Clinical outcomes; Clinical trials; Gene Expression; Gene Therapy; Growth factors; Humans; Immune response; Immunomodulation; Immunotherapy; Injection; Neoplasms - pathology; Oncolysis; Pharmacovigilance; Response Evaluation Criteria in Solid Tumors; Solid tumors; Tumor microenvironment; Tumors
• ISSN: 0929-1903; 1476-5500
• DOI: 10.1038/s41417-023-00720-0

AdAPT-001 is an oncolytic adenovirus (OAV) with a transforming growth factor beta (TGF-ß) trap, which neutralizes the immunosuppressive and profibrotic cytokine, TGF-ß. The aim or purpose of this phase 1 study was to assess the safety and tolerability and, secondarily, the efficacy of AdAPT-001 after single intratumoral injection (IT) (Part 1) and multidose IT injection (Part 2) in patients with superficially accessible, advanced refractory solid tumors. Part 1 enrolled 9 patients with a 3 + 3 single dose-escalation safety run-in involving 2.5 × 10 11 , 5.0 × 10 11 , 1.0 × 10 12 viral particles (vps). No dose-limiting toxicities or treatment-related serious adverse events (SAEs) were seen. In Part 2, a dose-expansion phase, 19 patients received AdAPT-001 at 1.0 × 10 12  vps until disease progression according to Response Evaluation Criteria in Solid Tumors or RECIST 1.1. The overall responses to treatment included confirmed partial responses (3), durable stable disease ≥ 6 months (5), and progressive disease (13). AdAPT-001 is well tolerated. Evidence of an anti-tumor effect was seen in both injected and uninjected lesions. The recommended Phase 2 dose was 1.0 × 10 12  vp administered by intratumoral injection once every 2 weeks. Combination of AdAPT-001 with a checkpoint inhibition is enrolling.