- [IMMUNOLOGY AND IMMUNOTHERAPY]
- [COMBINATION STRATEGIES FOR TRANSLATIONAL IMMUNOTHERAPY]
- [SOLID TUMOR]
- [ONCOGENES AND EFFECTOR TARGETS]
Intratumoral nanoplexed poly I:C BO-112 in combination with systemic anti-PD-1 for patients with anti-PD-1-refractory tumors
Iván Márquez-Rodas, Federico Longo, Maria E Rodriguez-Ruiz, Antonio Calles, Santiago Ponce, Maria Jove, Belén Rubio-Viqueira, Jose Luis Perez-Gracia, Ana Gómez-Rueda, Sara López-Tarruella, Mariano Ponz-Sarvise, Rosa Álvarez, Ainara Soria-Rivas, Enrique de Miguel, Rocío Ramos-Medina, Eduardo Castañon, Pablo Gajate, Cayetano Sempere-Ortega, Elisabeth Jiménez-Aguilar, M Angela Aznar, Aitana Calvo, Pedro P Lopez-Casas, Salvador Martín-Algarra, Miguel Martín, Dominique Tersago, Marisol Quintero, Ignacio Melero
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.
CITATION Sci Transl Med. 2020 Oct 14;12(565):eabb0391. doi: 10.1126/scitranslmed.abb0391.