A phase I/II study of LOAd703, a TMZ-CD40L/4-1BBL-armed oncolytic adenovirus, combined with nab-paclitaxel and gemcitabine in advanced pancreatic cancer.

• DOI: 10.1200/jco.2022.40.16_suppl.4138
• Publication Date: 2022-06-06T16:17:45Z
• Authors: Benjamin Leon Musher; Brandon George Sm...; Wasif Abidi; Mohamed Othman; Kalpesh Patel; Salmaan Jawaid; James Jing; Amanda Brisco; Jessica Wenthe; Emma Eriksson; Gustav J. Ullenhag; Linda Sandin; Bambi Grilley; Justyna Leja-Jarblad; Susan G. Hilsenbeck; Malcolm K. Brenner; Eric Keith Rowinsky; Angelica Sara Ing...
• Keywords: Oncolytic adenovirus

4138 Background: Due to its low tumor immunogenicity and immunosuppressive microenvironment, pancreatic ductal adenocarcinoma (PDAC) remains an immunotherapeutic challenge. LOAd703, oncolytic adenovirus with transgenes encoding TMZ-CD40L 4-1BBL, has been shown lyse cells selectively, induce anti-tumor cytotoxic T-cell responses, reduce myeloid-derived suppressor cell (MDSC) infiltration, regression in preclinical studies. Methods: In this phase I/II trial, patients unresectable or metastatic PDAC were treated intratumoral injections of LOAd703 standard intravenous nab-paclitaxel/gemcitabine (nPG) chemotherapy. Starting on cycle 1 day 15 nPG, was injected image guidance into the primary a metastasis every 2 weeks for 6 injections. event sustained control, subjects eligible receive up more Three dose levels investigated using BOIN escalation design. Primary endpoints safety feasibility. Results: Of 22 enrolled, 21 received at least injection, 18 3 (the priori definitions evaluability limiting toxicity [DLT] efficacy, respectively). injected, median age 61, 81% had stage IV disease, 57% already chemotherapy advanced disease. Median CA 19-9 1494. response evaluable subjects, level (5x10e10 VP), 4 (1x10e11 11 (5x10e11 VP). The most common adverse events (AEs) attributable fever, chills, nausea, increased liver enzymes. AEs short-lived grade 1/2, except transaminase elevation one subject receiving only DLT). Objective rate (ORR) among those highest 55% (5/11 subjects), thus meeting predefined criterion efficacy. Among all patients, overall 44%, disease control (DCR) 94%. decreased by ≥50% 61% patients. survival (OS) injection 8.7 months. proportion T effector memory after initiation on-protocol treatment (p = 0.0232) while regulatory 0.0410, p 0.0256, Conclusions: Combining nPG safe feasible. target met, treatment-emergent immune responses observed. A follow-up clinical trial combining anti-PDL-1 inhibitor atezolizumab is underway. Clinical information: NCT02705196.