Intratumoral nanoplexed poly I:C BO-112 in combination with systemic anti-PD-1 for patients with anti-PD-1-refractory tumors.
Márquez-Rodas I., Longo F., Rodriguez-Ruiz ME., Calles A., Ponce S., Jove M., Rubio-Viqueira B., Perez-Gracia JL., Gómez-Rueda A., López-Tarruella S., Ponz-Sarvise M., Álvarez R., Soria-Rivas A., de Miguel E., Ramos-Medina R., Castañon E., Gajate P., Sempere-Ortega C., Jiménez-Aguilar E., Aznar MA., Calvo A., Lopez-Casas PP., Martín-Algarra S., Martín M., Tersago D., Quintero M., Melero I.
Intratumoral therapies, especially Toll-like receptor agonists, can trigger both the innate and adaptive immune systems. BO-112 is a nanoplexed form of polyinosinic:polycytidylic acid (poly I:C) that induces local and systemic immunotherapeutic effects in mouse models. In a multicenter phase 1 clinical trial, repeated intratumoral administrations of BO-112 induced an increase in tumor cell necrosis and apoptosis, as well as augmented immune reactivity according to gene expression profiling. The first three cohorts receiving BO-112 as a monotherapy resulted in a recommended dose of 1 mg that could be safely repeated. Two grade 3 to 4 adverse reactions in the form of reversible thrombocytopenia were reported. In a fourth cohort of 28 patients with tumors that had primary resistance to anti-programmed cell death protein-1 (PD-1), the combination of intratumoral BO-112 with nivolumab or pembrolizumab was also well tolerated, and 3 patients (2 with melanoma and 1 with renal cell carcinoma) achieved partial responses, with 10 more patients having stable disease at 8 to 12 weeks. Thus, local BO-112 combined with a systemic anti-PD-1 agent might be a strategy to revert anti-PD-1 resistance.