polyinosinic:polycytidylic acid (BO-112)

P2, N=18, Terminated, Highlight Therapeutics | Phase classification: P2a --> P2

P2, N=60, Recruiting, Highlight Therapeutics | Not yet recruiting --> Recruiting

P2, N=60, Not yet recruiting, Highlight Therapeutics

Intratumoral injection of poly(I:C) sensitizes MHClow tumors to the antitumor effects of artLCMV-E7E6, resulting in a potent therapeutic synergy.

P1, N=14, Active, not recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2024 --> Jan 2025

P2, N=42, Active, not recruiting, Highlight Therapeutics | Trial completion date: Dec 2023 --> Aug 2024

P1, N=44, Completed, Highlight Therapeutics | Terminated --> Completed

This study demonstrates that local BO-112 immunotherapy and focal irradiation may act in synergy to achieve local tumor control. Irradiation plus BO-112 in one of the tumor lesions enhanced the therapeutic effects on distant irradiated lesions that were not injected with BO-112, suggesting strategies to treat oligometastatic patients with lesions susceptible to radiotherapy and with at least one tumor accessible for repeated BO-112 intratumoral injections.

P1, N=14, Active, not recruiting, Jonsson Comprehensive Cancer Center | Recruiting --> Active, not recruiting | N=20 --> 14

P1/2, N=30, Recruiting, Clinica Universidad de Navarra, Universidad de Navarra | Not yet recruiting --> Recruiting

P1/2, N=30, Ongoing, Clínica Universidad Navarra

Local-only therapy of BO-112 and RT yields a lymphocyte-dependent anti-tumor immune response in an immunotherapy-resistant model of UPS. Longitudinal analysis of locoregional immune responses and adoptive transfer experiments indicate that combination BO-112 and RT induces tumor-to-dLN myeloid trafficking that may bridge an adaptive response and confer therapeutic effect.

P1/2, N=30, Not yet recruiting, Clinica Universidad de Navarra, Universidad de Navarra

P2, N=42, Active, not recruiting, Highlight Therapeutics | Recruiting --> Active, not recruiting | Trial primary completion date: Jan 2022 --> Aug 2023

Clinically feasible co-injections of BO-112 and a STING agonist attain synergistic efficacy able to eradicate distant untreated tumor lesions.

Besides, PD‑L1 induced upregulation in response to BO-112, suggests the need to combine treatment with an anti-PD-1/PD-L1 agent. BO-112 has been injected intratumorally into the liver in 16 patients so far at two different studies: a phase I trial (NCT02828098, which included initially patients with solid tumors being treated with BO-112 monotherapy and, through subsequent amendment, in combination with anti PD-1 drugs in patients having developed progressive disease on these therapies, being treated with BO-112 plus the same checkpoint inhibitor) and a phase II study (NCT04508140), which is including patients with liver metastases from colorectal (CRC) or gastroesophageal (GE) origin, receiving IT BO-112 plus pembrolizumab. Liver is a challenging organ to achieve clinical benefit in terms of response; however, with IT BO-112 being administered in liver metastases from different tumors, there is a change in the TME with an increase in key biomarkers, which may overcome primary or secondary resistance to systemic immunotherapy.

P2, N=40, Recruiting, Highlight Therapeutics | Not yet recruiting --> Recruiting

Through independent mechanisms, overexpression of NLRC5 (nucleotide-binding oligomerization domain-like receptor family caspase recruitment domain containing 5) and intratumoral delivery of BO-112, a potent nanoplexed version of polyinosinic:polycytidylic acid (poly I:C), each restored the efficacy of ACT against B16-Jak1 tumors. In summary, we demonstrated that in the absence of tumor IFN signaling, MHC I expression is essential and sufficient for the efficacy of ACT. For tumors lacking MHC I expression due to deficient IFN signaling, activation of dsRNA sensors by BO-112 affords an alternative approach to restore the efficacy of ACT.

P2, N=40, Not yet recruiting, Bioncotech Therapeutics

P1, N=44, Terminated, Bioncotech Therapeutics | Trial completion date: Dec 2019 --> Jul 2020 | Active, not recruiting --> Terminated | Trial primary completion date: Aug 2019 --> Jul 2020

Genome-wide transcriptome analyses of injected tumor lesions were consistent with a marked upregulation of the type-I interferon pathway. Inspired by these data, intratumorally delivered BO-112 is being tested in cancer patients (NCT02828098).