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DRUG:

polyinosinic:polycytidylic acid (BO-112)

i
Other names: BO-112, BO 112, BO112, Poly I:C, nanoplexed Poly IC, nanoplexed Poly I:C
Associations
Company:
Highlight Therap
Drug class:
TLR3 agonist, EIF2AK2 activator, IFIH1 activator, PMAIP1 stimulant, RIG-I stimulant
Associations
6ms
SPOTLIGHT204: Clinical Trial to Evaluate BO-112 in Patients With Basal Cell Carcinoma (BCC) (clinicaltrials.gov)
P2, N=60, Recruiting, Highlight Therapeutics | Not yet recruiting --> Recruiting
Enrollment open
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polyinosinic:polycytidylic acid (BO-112)
6ms
New P2 trial
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polyinosinic:polycytidylic acid (BO-112)
7ms
Efficacy of LCMV-based cancer immunotherapies is unleashed by intratumoral injections of polyI:C. (PubMed, J Immunother Cancer)
Intratumoral injection of poly(I:C) sensitizes MHClow tumors to the antitumor effects of artLCMV-E7E6, resulting in a potent therapeutic synergy.
Journal • IO biomarker
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CD8 (cluster of differentiation 8) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • CCL3 (C-C Motif Chemokine Ligand 3) • IFNA1 (Interferon Alpha 1) • BATF3 (Basic Leucine Zipper ATF-Like Transcription Factor 3)
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polyinosinic:polycytidylic acid (BO-112)
9ms
NCI-2019-08556: Nivolumab and BO-112 Before Surgery for the Treatment of Resectable Soft Tissue Sarcoma (clinicaltrials.gov)
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
Trial completion date • Trial primary completion date • Surgery
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Opdivo (nivolumab) • polyinosinic:polycytidylic acid (BO-112)
10ms
KEYNOTE-B77: BO-112 With Pembrolizumab in Unresectable Malignant Melanoma (clinicaltrials.gov)
P2, N=42, Active, not recruiting, Highlight Therapeutics | Trial completion date: Dec 2023 --> Aug 2024
Trial completion date • Combination therapy
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BRAF (B-raf proto-oncogene) • CD4 (CD4 Molecule)
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Keytruda (pembrolizumab) • polyinosinic:polycytidylic acid (BO-112)
10ms
Exploratory Study of BO-112 in Adult Patients With Aggressive Solid Tumors (clinicaltrials.gov)
P1, N=44, Completed, Highlight Therapeutics | Terminated --> Completed
Trial completion • Combination therapy
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Keytruda (pembrolizumab) • Opdivo (nivolumab) • polyinosinic:polycytidylic acid (BO-112)
almost2years
Intratumoral BO-112 in combination with radiotherapy synergizes to achieve CD8 T-cell-mediated local tumor control. (PubMed, J Immunother Cancer)
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.
Journal • Combination therapy
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CALR (Calreticulin) • IFNAR1 (Interferon (alpha, beta and omega) receptor 1)
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polyinosinic:polycytidylic acid (BO-112)
almost2years
NCI-2019-08556: Nivolumab and BO-112 Before Surgery for the Treatment of Resectable Soft Tissue Sarcoma (clinicaltrials.gov)
P1, N=14, Active, not recruiting, Jonsson Comprehensive Cancer Center | Recruiting --> Active, not recruiting | N=20 --> 14
Enrollment closed • Enrollment change • Surgery
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CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
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Opdivo (nivolumab) • polyinosinic:polycytidylic acid (BO-112)
over2years
Noelia: Study of BO-112 With Radiotherapy and Nivolumab for Metastatic Refractory NSCLC (clinicaltrials.gov)
P1/2, N=30, Recruiting, Clinica Universidad de Navarra, Universidad de Navarra | Not yet recruiting --> Recruiting
Enrollment open • Combination therapy
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EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • CD4 (CD4 Molecule)
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Opdivo (nivolumab) • polyinosinic:polycytidylic acid (BO-112)
over2years
New P1/2 trial • Combination therapy
|
CD4 (CD4 Molecule)
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Opdivo (nivolumab) • polyinosinic:polycytidylic acid (BO-112)
over2years
Radiation and intratumoral activation of double-stranded RNA sensors redirects myeloid cells and primes adaptive immunity (AACR 2022)
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.
IO biomarker
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KRAS (KRAS proto-oncogene GTPase)
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KRAS G12D • KRAS G12
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polyinosinic:polycytidylic acid (BO-112)
over2years
Noelia: Study of BO-112 With Radiotherapy and Nivolumab for Metastatic Refractory NSCLC (clinicaltrials.gov)
P1/2, N=30, Not yet recruiting, Clinica Universidad de Navarra, Universidad de Navarra
New P1/2 trial • Combination therapy
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • CD4 (CD4 Molecule)
|
Opdivo (nivolumab) • polyinosinic:polycytidylic acid (BO-112)
over2years
KEYNOTE-B77: BO-112 With Pembrolizumab in Unresectable Malignant Melanoma (clinicaltrials.gov)
P2, N=42, Active, not recruiting, Highlight Therapeutics | Recruiting --> Active, not recruiting | Trial primary completion date: Jan 2022 --> Aug 2023
Enrollment closed • Trial primary completion date • Combination therapy
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BRAF (B-raf proto-oncogene) • CD4 (CD4 Molecule)
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Keytruda (pembrolizumab) • polyinosinic:polycytidylic acid (BO-112)
almost3years
Intratumoral co-injection of the poly I:C-derivative BO-112 and a STING agonist synergize to achieve local and distant anti-tumor efficacy. (PubMed, J Immunother Cancer)
Clinically feasible co-injections of BO-112 and a STING agonist attain synergistic efficacy able to eradicate distant untreated tumor lesions.
Clinical • Journal
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CD8 (cluster of differentiation 8) • STING (stimulator of interferon response cGAMP interactor 1) • TCF3 (Transcription Factor 3) • TLR3 (Toll Like Receptor 3) • IFIH1 (Interferon Induced With Helicase C Domain 1) • IFNAR1 (Interferon (alpha, beta and omega) receptor 1)
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polyinosinic:polycytidylic acid (BO-112)
over3years
[VIRTUAL] BO-112 as a modifier of the tumor microenvironment for liver metastases (AACR 2021)
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.
PD(L)-1 Biomarker • IO biomarker
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CD8 (cluster of differentiation 8) • TLR3 (Toll Like Receptor 3) • IFIH1 (Interferon Induced With Helicase C Domain 1)
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PD-L1 expression
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Keytruda (pembrolizumab) • polyinosinic:polycytidylic acid (BO-112)
over3years
SPOTLIGHT203: BO-112 With Pembrolizumab in Unresectable Malignant Melanoma (clinicaltrials.gov)
P2, N=40, Recruiting, Highlight Therapeutics | Not yet recruiting --> Recruiting
Clinical • Enrollment open • Combination therapy
|
BRAF (B-raf proto-oncogene) • CD4 (CD4 Molecule)
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Keytruda (pembrolizumab) • polyinosinic:polycytidylic acid (BO-112)
4years
Uncoupling interferon signaling and antigen presentation to overcome immunotherapy resistance due to JAK1 loss in melanoma. (PubMed, Sci Transl Med)
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.
Journal
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JAK2 (Janus kinase 2) • JAK1 (Janus Kinase 1)
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Hiltonol (poly-ICLC) • polyinosinic:polycytidylic acid (BO-112)
4years
Clinical • New P2 trial • Combination therapy
|
BRAF (B-raf proto-oncogene) • CD4 (CD4 Molecule)
|
Keytruda (pembrolizumab) • polyinosinic:polycytidylic acid (BO-112)
over4years
Exploratory Study of BO-112 in Adult Patients With Aggressive Solid Tumors (clinicaltrials.gov)
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
Clinical • Trial completion date • Trial termination • Trial primary completion date • Combination therapy
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IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha)
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Keytruda (pembrolizumab) • Opdivo (nivolumab) • polyinosinic:polycytidylic acid (BO-112)
over4years
Immunotherapeutic effects of intratumoral nanoplexed poly I:C. (PubMed, J Immunother Cancer)
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).
Journal
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CD8 (cluster of differentiation 8)
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polyinosinic:polycytidylic acid (BO-112)