Abstract CT122: Trial in progress: Phase 1 study of an oncolytic virus, ASP1012, in adults with advanced solid tumors

Abstract Background: Conventional therapies still have limited curative efficacy for many advanced solid tumors, prompting research into immunotherapies including oncolytic viruses. ASP1012, a double-stranded DNA oncolytic and immunotherapeutic vaccinia virus encoding a leptin-interleukin 2 fusion protein that selectively replicates in cancer cells, is being developed for the treatment of patients with locally advanced or metastatic (la/m) solid tumors. Methods: This Phase 1, first-in-human, open-label, multicenter dose escalation (Part 1) and dose expansion (Parts 2/3) study (NCT06171178) of ASP1012 alone or + pembrolizumab will evaluate the safety, tolerability, maximum tolerated dose (MTD), and/or recommended Phase 2 dose (RP2D) in US adults. Key inclusion criteria are measurable disease with ≥ 1 biopsy site (except colorectal [CRC] and ovarian cancer [OC] in Part 3) and Eastern Cooperative Oncology Group (ECOG) performance status of 0/1. Part 1 includes patients with previously treated la/m solid tumors; Part 2, patients with previously treated cutaneous melanoma or solid tumors, or treatment-naïve melanoma amenable to resection; and Part 3, patients with previously treated gastric cancer, CRC, OC, or other solid tumors based on antitumor activity or biomarker response from Parts 1 or 2. Primary endpoint is safety and tolerability, assessed by dose-limiting toxicities (DLTs), adverse events, clinical evaluations, and ECOG performance status. Key secondary endpoints include pharmacokinetics/pharmacodynamics; viral DNA in urine, saliva, and feces; viral DNA in tumors; antidrug antibody detection; objective response rate; duration of response; disease control rate; overall survival, and progression-free survival/relapse-free survival per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune-based RECIST; and changes from baseline in CA-125 (in OC) and ctDNA (in CRC). In Part 1, DLTs will determine MTD and/or candidate RP2D in patients receiving 1 of 4 escalating doses of ASP1012 administered intravenously (IV) once-weekly (Q1W) for a limited number of doses in 21-day cycles. In Part 2, patients with previously treated melanoma with relapse or progression on prior therapy will receive ASP1012 monotherapy at RP2D (Day 1; IV Q1W or every 2 weeks for a limited number of doses); patients with previously treated solid tumors will receive ASP1012 at RP2D [-1] or RP2D + pembrolizumab (Day 8; IV 200 mg every 3 weeks for 3 doses). If an acceptable safety profile is demonstrated in the combination treatment cohort of Part 2, patients with treatment-naïve melanoma amenable to resection will receive ASP1012 at RP2D pembrolizumab. Part 3 will evaluate ASP1012 (± pembrolizumab) at RP2D in multiple solid tumors. Safety follow-up will occur 30 days posttreatment, posttreatment follow-up every 6 weeks, and survival follow-up ≥ every 12 weeks ± 2 weeks. Study enrollment is currently ongoing in the US. Citation Format: Douglas Laux, Olumide Gbolahan, Yohei Okada, Toru Kakinuma, Gerald Koelsch, Ziwen Wei, Paul Lee, Markus Vallaster, Anthony F. Shields. Trial in progress: Phase 1 study of an oncolytic virus, ASP1012, in adults with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT122.