Binary oncolytic adenovirus in combination with HER2-specific autologous CAR VST for treatment of advanced HER2-positive solid tumors (VISTA).

• DOI: 10.1200/jco.2024.42.16_suppl.tps2679
• Publication Date: 2024-07-02T00:45:11Z
• Authors: Shalini Makawita; Jerry M Gibbs; Dustin R. McFadden; Caroline Porter; Amanda Rosewell Shaw; Catherine Robertson; Mae Louise Woods; Tao Wang; Bambi J Grilley; Helen E Heslop; Malcolm K Brenner; Masataka Suzuki
• Keywords: Solid tumor

TPS2679 Background: Urgent therapies are needed for patients with refractory Human Epidermal Growth Factor Receptor 2 (HER2) positive solid malignancies. Our group has previously shown potent antitumor effect of a binary oncolytic/helper-dependent adenovirus (CAdVEC) dual expression IL-12 and PD-L1 blocker. Initial preclinical clinical studies direct tumor injection CAdVEC it to be safe result in increased infiltration CD8 T cells into the microenvironment, on locoregional distant metastatic sites. 1 Based these results, we describe an ongoing study addition HER2-specific autologous chimeric antigen receptor (CAR)-T cell therapy CAdVEC. Methods: This is single arm, dose escalation phase I trial guided by Bayesian Optimal Interval Design (BOIN) advanced HER2 tumors. Patients who deemed unsuitable curative treatments progressed after at least one standard first line eligible. positivity determined IHC defined as ≥2+. required have site appropriate intratumor radiographically measurable disease per RECIST v1.1. autoimmune requiring systemic corticosteroids greater than 10mg/day those active/untreated CNS metastasis excluded. will receive increasing doses alone (first two levels) or combination specific CAR-T (dose levels 3-7). A total 45 planned. The primary endpoint evaluate safety maximum tolerated assessed incidence limiting toxicities (DLT) CAR cells. Secondary endpoints include anti-tumor activity measured overall response rate (ORR), control (DCR), median progression free survival (PFS) (OS). Exploratory assessing immunogenicity determining impact treatment cellular humoral immunity, well long-term persistence functional status T-cells. Correlative analysis antibodies outcomes immunological findings also currently enrolling. 1. Wang D, Porter CE, Lim B, et al: Science Advances 9, 2023. Clinical information: NCT03740256 .