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

BO-112 Plus Pembrolizumab for Patients With Anti-PD-1-Resistant Advanced Melanoma: Phase II Clinical Trial SPOTLIGHT-203. (PubMed, J Clin Oncol) - P2 | "The clinical trial has met its primary end point (ORR) making BO-112 with pembrolizumab a potential strategy to revert anti-PD-1 resistance in patients with MEL. PFS results are in line with other clinical trials in anti-PD-1-resistant scenario, with promising OS data."

Journal • P2 data • Melanoma • Oncology • Solid Tumor

Predictors of clinical and pathological response in patients with basal cell carcinoma treated with BO-112, a novel intralesional treatment (EADO 2026) - No abstract available

Clinical • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

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 2027 ➔ Jan 2028 | Trial primary completion date: Jan 2026 ➔ Jan 2027

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

Neoadjuvant BO-112 and hypofractionated radiation therapy with or without nivolumab in soft tissue sarcoma: preclinical and phase 1 results. (PubMed, Cancer Discov) - "BO-112 and RT reprogrammed tumor-associated myeloid cells toward antigen-presenting states, promoted clonal replacement by less exhausted T cells, and enhanced malignant cell depletion compared to standard RT. These immunologic changes coincided with encouraging disease control in a small, high-risk cohort, supporting further clinical development."

Journal • P1 data • Preclinical • Cardiovascular • CNS Disorders • Immunology • Myasthenia Gravis • Myositis • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

SPOTLIGHT 204: Clinical Trial to Evaluate BO-112 in Patients With Basal Cell Carcinoma (BCC) (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: Highlight Therapeutics | Recruiting ➔ Active, not recruiting

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

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

KEYNOTE-B77: BO-112 With Pembrolizumab in Unresectable Malignant Melanoma (clinicaltrials.gov) - P2 | N=42 | Completed | Sponsor: Highlight Therapeutics | Active, not recruiting ➔ Completed

Trial completion • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • BRAF • CD4

Erratum: BO-112 Plus Pembrolizumab for Patients With Anti-PD-1-Resistant Advanced Melanoma: Phase II Clinical Trial SPOTLIGHT-203. (PubMed, J Clin Oncol) - No abstract available

Journal • P2 data • Melanoma • 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 | 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

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