Abstract LOAd703, a tumor microenvironment (TME) gene engineering, tumor-selective oncolytic adenovirus, was combined with nab-paclitaxel (nP), gemcitabine (G), and atezolizumab in a Phase I/II trial for patients with pancreatic cancer (PC). Encoding a trimerized, membrane-bound CD40L and 4-1BBL, LOAd703 is designed to expand Th1 type tumor-reactive cytotoxic T cells in vivo. In LOKON001 Arm 1, the combination of intratumorally injected LOAd703 and intravenous (IV) nPG was shown to be safe in patients with advanced PC, with successful reprogramming of the TME and expansion of tumor-reactive T cells. In LOKON001 arm 2 (preliminary data reported), 24 patients with advanced PC (stage 3, n=2; stage 4, n=22) received up to 12 biweekly intratumoral injections of LOAd703 (1x10e11 VP, n=12; 5x10e11 VP, n=12), standard nPG (nabpaclitaxel 125 mg/m2 plus gemcitabine 1000 mg/m2 IV on days 1, 8, and 15 of a 28-day cycle), and the PD-L1 inhibitor atezolizumab (1680 mg IV on day 1 of each 28-day nPG cycle). Primary objectives were safety and feasibility. Median age at enrollment was 60 years (IQR: 53-65), and 46% of patients had received prior systemic therapy for advanced PC. Patients received a median of 7 (IQR: 5-10) LOAd703 injections and 6 (IQR: 4-9) atezolizumab infusions and initiated a median of 7 (IQR: 4-9) chemotherapy cycles. Treatment was well-tolerated, with the most common grade 1-2 adverse events attributed to LOAd703 being fever (67%), chills (46%), fatigue (25%), headache (21%), and hypotension (17%). Eight grade 3/4 events were reported possibly related to both LOAd703 and atezolizumab of which three were kidney-related toxicity (a grade 3- and a grade 4 event of acute kidney injury in one patient and a grade 3 event of membranoproliferative glomerulonephritis in a second patient). The remainder of grade 3/4 adverse events were attributed to underlying disease, chemotherapy, atezolizumab, or other. Among evaluable patients (n=24), overall response rate (ORR) and disease control rate (DCR) were 29% (CI 95% 15-49) and 88% (CI 95% 69-96), respectively. Among patients receiving first-line (1L) therapy, ORR and DCR were 38% (CI 95% 18-65) and 85% (CI 95% 58-97), respectively. Three patients (all of whom were 1L) had complete responses (CR), yielding an overall CR rate of 13% (23% among 1L patients). Median overall survival (OS) was 9 months (CI 95% 7-14) among all evaluable patients and 15. 5 months (CI 95% 7-24) among 1L patients. Tumor mRNA profiling showed upregulation of adaptive immune response biomarkers and identified signatures linked to response and survival. In conclusion, combining LOAd703 with nPG and atezolizumab was safe, induced a favorable adaptive immune profile, and showed encouraging antitumor activity warranting for further clinical development in a randomized trial. Study registration: NCT02705196. Lokon Pharma sponsored the study and Hoffmann La Roche supported the study with atezolizumab supply. Citation Format: Benjamin L. Musher, Linda C. Sandin, Wasif Abidi, Kalpesh Patel, Salmaan Jawaid, Gary Horn, Neal Savjani, Tannaz Armaghany, Shalini Makawita, Monica A. Francois, Mengfen Wu, Justyna Leja Jarblad, Jessica Wenthe, Emma Eriksson, Sue G. Hilsenbeck, Malcolm K. Brenner, Angelica Loskog. A phase I/II trial evaluating LOAd703 in combination with nab-paclitaxel, gemcitabine, and atezolizumab for advanced pancreatic cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86 (8Suppl): Abstract nr CT031.
Musher et al. (Fri,) studied this question.