The AGADIR study is a multi-cohort, multicenter, open-label Phase II trial in patients with advanced cancers that combines the new TLR7/8 agonist BDB001 with atezolizumab and stereotactic body radiation (SBRT). The primary objectives of the trial is to determine the disease control rate, which is defined as the proportion of individuals who have a full response, a partial response, or stable illness as defined by modified RECIST v1.1 within 24 weeks after therapy initiation, objective response, progression-free survival, overall survival, and safety are secondary endpoints. For translational research, all patients had sequential blood and tissue samples.
In total, thirty-two patients were enrolled across three centers for the study. Patients with advanced pancreatic cancer were included in cohort A. BDB001 was given intravenously at 0.75 mg/m2 on days 1, 8, and 15 of cycles 1, 2, and 3. Then every three weeks, beginning with cycle 4 on day 1. Every three weeks, 1200 mg of atezolizumab was administered. SBRT for at least one metastatic lesion began at least one week after the initial atezolizumab injection and no later than cycle 2 day 1.
The evaluable population for efficacy comprised twenty-five patients. The best tumor responses were proven partial response, stable disease, and progressing disease in 2 (8%), 7 (28%), and 14 (56%), respectively. The disease control rate (DCR) was determined to be 36.0%.
KOL insights
“BDB001, the first in its class, TLR7/8 has a great future when combined with radiation therapy. The analysis of the tissue biopsy samples would further tell us about the promising efficacy and safety parameters.” -Expert Opinion.
Conclusion
Pancreatic adenocarcinoma is the most common type of pancreatic cancer. Immune checkpoint inhibitors like PD1/PDL1 antagonists are ineffective against this kind.
Toll-like receptor (TLR) agonists are being developed as potential immune-oncology treatments because of their powerful immunostimulatory effects. These are essential regulators of inflammatory pathways in the gut, modulating immune responses to a wide range of pathogen-derived ligands and connecting adaptive and innate immunity. Radiation treatment combined with TLR agonists has been proven in preclinical studies to improve antitumor immunity. As the study has met its primary endpoint of DCR, the future is promising as far as enhancement of the anti-tumor activity is concerned. The analysis of the sequential plasma and tissue biopsy samples is still underway
