Abstract A074: A novel nano-formulated taxoid (RP-001) enhances T-cell infiltration and prolongs survival in preclinical models of pancreatic ductal adenocarcinoma

Abstract Pancreatic ductal adenocarcinoma (PDA) is a highly lethal malignancy with a poor prognosis. Current therapies, including immunotherapy, have demonstrated limited efficacy, highlighting the urgent need for novel therapeutic agents. This study aimed to evaluate the therapeutic potential of a novel taxoid (DHA-SBT1214) formulated in an oil-in-water nanoemulsion (RP-001), administered alone or in combination with immune checkpoint inhibition, in enhancing immune cell infiltration and improving outcomes in preclinical models of PDA. To this end, four-month-old female LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx1-Cre (KPC) mice (n=6/group) were randomized to receive vehicle control (empty nanoemulsion, IV weekly), RP-001 (10 mg/kg, IV weekly), anti-PD-1 antibody (200 µg, IP twice weekly), or a combination of RP-001 and anti-PD-1 for three weeks. Following treatment, pancreatic tissues were collected for comprehensive immunophenotyping of tumor-infiltrating lymphocytes using flow cytometry, with markers including CD45, CD3, CD4, CD8, and PD-1. RP-001 efficacy was assessed in an orthotopic model of pancreatic cancer (n=10/group) and in a survival study involving male and female KPC mice treated with vehicle or RP-001 (10 mg/kg, IV weekly) for four weeks. In KPC mice, combination treatment with RP-001 and anti-PD-1 significantly increased CD4+ T cell infiltration compared to control. Both RP-001 monotherapy and combination therapy enhanced CD8+ T cell infiltration, indicating a direct immunomodulatory effect. Importantly, no significant body weight loss was observed in any treatment group, supporting the safety of these regimens. In the orthotopic model, RP-001 significantly reduced tumor weight by 41.2% after three weeks. Additionally, RP-001 treatment significantly prolonged median survival in KPC mice compared to vehicle-treated controls in both males and females. In conclusion, RP-001 exhibits strong antitumor activity, enhances immune cell infiltration, and is well-tolerated in multiple preclinical models of PDA. These findings support further investigation of RP-001 as a promising therapeutic candidate for PDA. Acknowledgement: [NCI R01 grant] Citation Format: Laura Musumeci, Irena Krga, Lizbeth Flores, Allison Ehrlich, Satveer Jagwani, Edward Kim, James E. Egan, Mansoor M. Amiji, Gerardo G. Mackenzie. A novel nano-formulated taxoid (RP-001) enhances T-cell infiltration and prolongs survival in preclinical models of pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr A074.