polyinosinic:polycytidylic acid (BO-112) / Highlight Therap - LARVOL DELTA

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 | Sponsor: Jonsson Comprehensive Cancer Center | Trial completion date: Jan 2026 ➔ Jan 2027 | Trial primary completion date: Jan 2025 ➔ Jan 2026

Trial completion date • Trial primary completion date • Brain Cancer • Fibrosarcoma • Leiomyosarcoma • Liposarcoma • Neurofibrosarcoma • Oncology • Osteosarcoma • Retroperitoneal Sarcoma • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Spindle Cell Sarcoma • Synovial Sarcoma • Undifferentiated Pleomorphic Sarcoma

KEYNOTE-A06: Study of BO-112 With Pembrolizumab for Colorectal or Gastric/GEJ Cancer With Liver Metastasis (clinicaltrials.gov) - P2 | N=18 | Terminated | Sponsor: Highlight Therapeutics | Phase classification: P2a ➔ P2

Combination therapy • Phase classification • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Hepatology • Oncology • Solid Tumor

Targeting myeloid cells with BO-112 engages T cell immunity in combination with radiotherapy and checkpoint blockade in preclinical models and a phase 1 neoadjuvant clinical trial (SITC 2024) - P1 | "In a Phase I neoadjuvant trial, patients with STS received intratumoral BO-112, hypofractionated RT ± nivolumab followed by surgery. Targeting myeloid cells with BO-112 may be a complementary strategy to promoting T cell responses in STS. Ethics Approval Ethics approval was obtained for the Phase I clinical trial (NCT02828098 approved the UCLA Institutional Review Board #19-000419) and animal research (ARC-2017-088 approved by the UCLA Institutional Animal Care and Use Committee/Animal Research Committee (ARC)) Clinical trial participants gave informed consent before enrolling and participating in the trial."

Checkpoint block • Checkpoint inhibition • Combination therapy • IO biomarker • P1 data • Preclinical • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • CD8 • IFNG • KRAS

PHASE 1 STUDY OF INTRATUMORAL BO-112 AND NIVOLUMAB IN RESECTABLE SOFT TISSUE SARCOMA UNDERGOING HYPOFRACTIONATED PREOPERATIVE RADIOTHERAPY (CTOS 2024) - No abstract available

P1 data • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

SPOTLIGHT204: Clinical Trial to Evaluate BO-112 in Patients With Basal Cell Carcinoma (BCC) (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Highlight Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Nodular Basal Cell Carcinoma

SPOTLIGHT204: Clinical Trial to Evaluate Safety, Tolerability and Preliminary Efficacy of BO-112 in Patients With BCC (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Highlight Therapeutics

New P2 trial • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Nodular Basal Cell Carcinoma

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."

IO biomarker • Journal • CNS Disorders • Infectious Disease • Oncology • BATF3 • CCL3 • CD8 • CXCL10 • IFNA1

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 | Sponsor: Jonsson Comprehensive Cancer Center | Trial completion date: Jan 2025 ➔ Jan 2026 | Trial primary completion date: Jan 2024 ➔ Jan 2025

Surgery • Trial completion date • Trial primary completion date • Brain Cancer • Fibrosarcoma • Leiomyosarcoma • Liposarcoma • Neurofibrosarcoma • Oncology • Osteosarcoma • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Spindle Cell Sarcoma • Synovial Sarcoma • Undifferentiated Pleomorphic Sarcoma

KEYNOTE-B77: BO-112 With Pembrolizumab in Unresectable Malignant Melanoma (clinicaltrials.gov) - P2 | N=42 | Active, not recruiting | Sponsor: Highlight Therapeutics | Trial completion date: Dec 2023 ➔ Aug 2024

Combination therapy • Trial completion date • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • BRAF • CD4

Exploratory Study of BO-112 in Adult Patients With Aggressive Solid Tumors (clinicaltrials.gov) - P1 | N=44 | Completed | Sponsor: Highlight Therapeutics | Terminated ➔ Completed

Combination therapy • Trial completion • Oncology • Solid Tumor

Efficacy of intratumoral BO-112 with systemic pembrolizumab in patients with advanced melanoma refractory to anti-PD-1-based therapy: Final results of SPOTLIGHT203 phase 2 study (AACR 2022) - P1, P2 | "The primary efficacy endpoint has been met. Additionally, disease control (PR+CR+SD) is meaningful and durable in a population with no current standard treatment options. Very high LDH levels (LDH >3xULN) and acral mel could predict poor outcome."

Clinical • IO biomarker • P2 data • Melanoma • Oncology • Solid Tumor • BRAF • CD8

Intratumoral neoadjuvant immunotherapy based on the BO-112 viral RNA mimetic. (PubMed, Oncoimmunology) - "The anti-tumor efficacy of this neoadjuvant immunotherapy approach depended on the presence of antigen-specific effector CD8 T cells and cDC1 antigen-presenting cells. Since BO-112 has been successful in phase-two clinical trials for metastatic melanoma, these results provide a strong rationale for translating this pre-surgical strategy into clinical settings, especially in combination with standard-of-care checkpoint inhibitors."

Journal • Melanoma • Oncology • Solid Tumor

BO-112 and Pembrolizumab for the Treatment of PD-1/PD-L1 Refractory Liver Cancer (clinicaltrials.gov) - P1 | N=1 | Terminated | Sponsor: Jonsson Comprehensive Cancer Center | N=15 ➔ 1 | Trial completion date: Oct 2025 ➔ Mar 2023 | Suspended ➔ Terminated | Trial primary completion date: Oct 2024 ➔ Mar 2023; Withdrawn by sponsor

Combination therapy • Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor

Intratumoral BO-112 in combination with pembrolizumab in patients with melanoma and skin only metastases; subgroup analysis of BOT112-03 clinical trial (EADO 2022) - No abstract available

Clinical • Combination therapy • Melanoma • Oncology • Solid Tumor

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."

Combination therapy • Journal • Breast Cancer • Oncology • Solid Tumor • Transplantation • CALR • IFNAR1

BO-112 and Pembrolizumab for the Treatment of PD-1/PD-L1 Refractory Liver Cancer (clinicaltrials.gov) - P1 | N=15 | Suspended | Sponsor: Jonsson Comprehensive Cancer Center | Recruiting ➔ Suspended

Combination therapy • Trial suspension • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor

KEYNOTE-A06: Study of BO-112 With Pembrolizumab for Colorectal or Gastric/GEJ Cancer With Liver Metastasis (clinicaltrials.gov) - P2a | N=18 | Terminated | Sponsor: Highlight Therapeutics | N=69 ➔ 18 | Trial completion date: Jul 2023 ➔ Dec 2022 | Recruiting ➔ Terminated | Trial primary completion date: Jul 2023 ➔ Dec 2022; Low recruitment rate

Combination therapy • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Solid Tumor

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 | Sponsor: Jonsson Comprehensive Cancer Center | Recruiting ➔ Active, not recruiting | N=20 ➔ 14

Enrollment change • Enrollment closed • Brain Cancer • Fibrosarcoma • Immunology • Leiomyosarcoma • Liposarcoma • Neurofibrosarcoma • Oncology • Osteosarcoma • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Spindle Cell Sarcoma • Synovial Sarcoma • Undifferentiated Pleomorphic Sarcoma • CD4 • CD8

Intratumoral BO-112, a double-stranded RNA (dsRNA), alone and in combination with systemic anti-PD-1 in solid tumors (ESMO 2018) - P1; "C3: 0.6 mg IT BO-112 qw x 2-3 doses (N=3); C4: Pts with primary refractory tumors to anti PD-1 were treated with 1mg IT BO112 qw x 2 or 3 doses before continuing nivolumab or pembrolizumab combined with BO-112, until progression, limiting toxicity or up to 1y (N=12). IT BO-112 has demonstrated a manageable safety profile alone and combined with anti PD-1. Its mechanism of action comprises direct antitumor effect, innate and adaptive immune system activation. Combination with anti PD-1 is feasible in anti PD-1 refractory pts."

Combination therapy • IO biomarker • Late-breaking abstract • PD(L)-1 Biomarker • Melanoma • Renal Cell Carcinoma

Radiomic features in tumor assessment, preliminary results from a phase 2 study of intratumoral administration of BO-112 with pembrolizumab in patients with anti PD1 refractory melanoma (AACR 2022) - P2 | "Imaging biomarkers provide a large number of quantitative image features with a wide span of information, from size to heterogeneity of the tissue which may be indicator of tumor progression and immune infiltrate. In the analysis of radiomics features, delta GLRLM low grey-level zone emphasis was sensitive to the tumoral changes happening in injected lesions at week 8. This might add insights into the imaging-based evaluation of immune infiltration in intratumoral immunotherapy and the creation of associated imaging biomarkers panels."

Clinical • IO biomarker • P2 data • Melanoma • Oncology • Solid Tumor

Combination of intratumoural double-stranded RNA (dsRNA) BO-112 with systemic anti-PD-1 in patients with anti-PD-1 refractory cancer (ESMO-IO 2019) - P1; " BO-112 was combined with anti PD-1 in 28 pts with solid tumors primarily resistant to anti PD-1 (nivolumab or pembrolizumab). BO-112 combined with anti PD-1 shows a manageable safety profile, direct antitumor effects and innate and adaptive immune system activation. Efficacy analyses suggest potential to reverse primary resistance to anti-PD1 treatment. Studies in other indications, including combination with radiotherapy, are planned.Legal entity responsible for the study: Bioncotech Therapeutics."

Clinical • IO biomarker • Genito-urinary Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor

Preliminary results of a phase 2 study of intratumoral administration of BO-112 with pembrolizumab in patients with advanced melanoma that have progressive disease on anti-PD-1-based therapy (SITC 2021) - P2 | "BO-112 is able to increase PD-L1 expression in tumor cells and increase CD8-T cell infiltrates. Trial Registration NCT04570332"

Clinical • IO biomarker • Late-breaking abstract • P2 data • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • BRAF • CD8

Correlation of biomarkers and clinical benefit of intratumoral BO112 and pembrolizumab in patients with anti PD1 refractory melanoma (AACR 2022) - P1, P2 | "Patients basal mutant BRAF/NRAS could have more probability of benefit from BO-112 and pembrolizumab combination. PD-L1 and/or CD8 increase is an early marker of response. These findings could help to select patients in future clinical trials."

Biomarker • Clinical • IO biomarker • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • BRAF • CD8 • NRAS • SETD2 • TMB • TP53

Local immunotherapy: translation of the dsRNA analog BO112 (AACR-NCI-EORTC 2022) - No abstract available

Oncology

Intratumoral dsRNA Sensor Activation Redirects Radiation-Associated Myeloid Cells to Ignite Local and Systemic Anti-Tumor Immunity in Undifferentiated Pleomorphic Sarcoma (ASTRO 2022) - "Intratumoral BO-112 preferentially targets myeloid cells and augments the response to radiation in an ICB-resistant model of UPS. Reprogramming RT-induced intratumoral myeloid cells toward an antigen-presenting fate and their redirection to the lymph node may bridge an adaptive T cell response and lead to enhanced tumor control."

Hematological Malignancies • Immune Modulation • Inflammation • Oncology • Sarcoma • Solid Tumor • Undifferentiated Pleomorphic Sarcoma • CD4 • CD8 • ITGAX • KRAS