First in class TLR7/8 agonist BDB001 combined with atezolizumab and stereotactic body radiation therapy in patients with advanced pancreatic adenocarcinoma: Results from the AGADIR study

4153 Background: Pancreatic adenocarcinoma is refractory to immune checkpoint inhibitors such as PD1/PDL1 antagonists. Investigating alternative immunotherapeutic approaches is a crucial need for this devastating disease. The potent immunostimulatory effects of Toll-like receptor (TLRs) have spurred efforts aimed at the development of TLR agonists as new immune-oncology agents. Radiation therapy combined with TLRs agonists has been shown to enhance antitumor immunity in the preclinical setting. Methods: AGADIR is a multi-cohort, phase 2, multicenter, open-label study investigating the novel TLR 7/8 agonist BDB001 combined with atezolizumab and stereotactic body radiotherapy (SBRT) in patients with advanced cancers. Cohort A enrolled patients with advanced pancreatic adenocarcinoma. BDB001 was administered IV at the dose of 0.75 mg/m² on days 1, 8, and 15 of cycles 1, 2, and 3. Then from cycle 4 on day 1 every 3 weeks. Atezolizumab was given at the dose of 1200 mg every 3 weeks. SBRT of at least one metastatic lesion was started at least one week after the first administration of atezolizumab and at the latest before the Cycle 2 Day 1. The primary endpoint is disease control rate defined as the proportion of participants with complete response, partial response or stable disease, as per adapted RECIST v1.1, observed within 24 weeks of treatment onset. Secondary endpoints include objective response, progression-free survival, overall survival and safety. All patients underwent sequential blood and tissue sampling for translational studies. Results: Between July 2021, and June 2022, 32 pts were enrolled in 3 centers (14 male, 18 female). Median age was 64 years (range 38 – 78). Median number of previous treatment lines was 1 (range 1 – 5). The most common treatment related adverse events were grade 1/2 asthenia, chills and fever. No death was related to the treatment. Among the 21 patients for whom central review was performed at the time of this writing, best tumor response was confirmed partial response, stable disease and progressive disease in 2 (9.5%), 6 (28.5%) and 13 (62.0%) patients respectively. The disease control rate was 38.0% (95%CI 18.1-61.5). Conclusions: The AGADIR study met its first endpoint for disease control rate in patients with advanced pancreatic cancer. Efficacy data on the whole cohort of patients and full biomarkers analyses will be presented at the meeting. Clinical trial information: NCT03915678 .