BI 1831169 / Boehringer Ingelheim - LARVOL DELTA

A Study to Test How Well Different Doses of BI 1831169 in Combination With an Anti-PD1 Antibody Are Tolerated in Japanese People With Different Advanced Cancers (clinicaltrials.gov) - P1 | N=46 | Suspended | Sponsor: Boehringer Ingelheim | Not yet recruiting ➔ Suspended

Trial suspension • Oncology • Solid Tumor

Oncolytic virus-delivered GSDME: Unlocking pyroptosis to improve dendritic cell function and amplify cytotoxic T cell response. (PubMed, Mol Ther Oncol) - "Thus, VSV-GP-GSDME combines VSV-GP's oncolytic activity with GSDME-mediated pyroptosis to induce anti-tumor immunity. This dual mechanism broadens applicability across diverse tumors, offering a promising strategy to enhance immunogenicity."

IO biomarker • Journal • Oncology • CASP3 • CD8 • GSDME

A Study to Test How Well Different Doses of BI 1831169 in Combination With an Anti-PD1 Antibody Are Tolerated in Japanese People With Different Advanced Cancers (clinicaltrials.gov) - P1 | N=46 | Not yet recruiting | Sponsor: Boehringer Ingelheim | Initiation date: Jun 2026 ➔ Aug 2027

Trial initiation date • Oncology • Solid Tumor

An ex vivo permissivity assay to assess replication of the oncolytic virus VSV-GP in patient-derived tumor samples. (PubMed, Oncogene) - "Based on the results of our comprehensive testing and by employing VSV-GP-NanoLuc-Katushka, we were able to establish a semi-automated permissivity assay with minimal hands-on time, allowing robust and real-time tracking of viral replication in patient-derived tumor samples. Given the urgent demand for innovative cancer treatments, this novel permissivity assay could be applied to select patients with tumors permissive to OV replication and might thus also show an enhanced clinical response."

IO biomarker • Journal • Preclinical • Oncology

A Study to Test Different Doses of BI 1831169 Alone and in Combination With an Anti-PD-1 Antibody in People With Different Types of Advanced Cancer (Solid Tumors) (clinicaltrials.gov) - P1 | N=190 | Suspended | Sponsor: Boehringer Ingelheim | Recruiting ➔ Suspended

Monotherapy • Trial suspension • Oncology • Solid Tumor

TcE armed oncolytic virus VSV-GP combines oncolysis and T-cell retargeting for improved efficacy (AACR 2024) - "Virus fitness was maintained for VSV-GP encoding the TcE molecule. Using co-culture assays, we demonstrated that EpCAM-TcE molecule is successfully expressed by VSV-GP and can activate both CD4+ and CD8+ T cells resulting in proliferation, degranulation, and cytokine secretion. Furthermore, we validated the concept using patient-derived HNSCC tumor slices which are representative of complex human tumor ecosystems."

Clinical • Oncolytic virus • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD34 • CD8 • IFNG • TNFA

Protein Priming Followed by a Replication-Competent VSV-GP Vector Boost Induces Sustained Immune Control in Therapeutic Hepatitis B Vaccination. (PubMed, Vaccines (Basel)) - "Background/Objectives: Eliciting robust immune responses against the hepatitis B virus (HBV) through therapeutic vaccination holds promise for curing chronic hepatitis B. We previously developed the heterologous protein prime/viral vector boost clinical vaccine candidate, TherVacB. Long-term analyses performed 10 weeks after the last vaccination further demonstrated that a single protein-prime/VSV-GP-HBs/c boost was sufficient to achieve sustained antiviral control. These findings identify VSV-GP-HBs/c as an effective boost vector for therapeutic hepatitis B vaccination and establish protein priming followed by a single viral vector boost as an optimal strategy for sustained antiviral immunity."

Journal • Hepatitis B • Infectious Disease • Inflammation • CD4 • CD8 • IFNG

The oncolytic vesicular stomatitis virus VSV-GP shows profound oncolytic activity in NUT-carcinoma cell lines. (PubMed, Mol Ther Oncol) - P1 | "While synthesis of intrinsic interferon (IFN)-β was found to be suppressed in VSV-GP-infected NC cell lines, intracellular IFN-β signaling was functional. Since VSV-GP is a promising compound for virotherapy of NC patients, exploration of virus-induced immunogenicity and identification of resistance mechanisms could pave the way for additional combination treatment regimes in NC."

Journal • Preclinical • Infectious Disease • NUT Midline Carcinoma • Oncology • IFNB1 • NUTM1

Tropism Profiling of Lentiviral Vector Pseudotypes in Diverse Brain Tumor Models. (PubMed, Pharmaceutics) - "VSV-GP appears most suitable for medulloblastoma and lung metastases, FuG-B2 for melanoma metastases, and both for GBM and DIPG gene therapy applications. The study provides crucial guidance for translating lentiviral gene therapy to clinical applications, supporting personalized treatment strategies based on tumor-specific vector tropism profiles."

Journal • Preclinical • Brain Cancer • Diffuse Intrinsic Pontine Glioma • Gene Therapies • Glioblastoma • Glioma • Medulloblastoma • Melanoma • Oncology • Solid Tumor

Heterologous combinations of VSV-GP and native-like trimers elicit autologous Tier 2 HIV antibodies in rabbits. (PubMed, NPJ Vaccines) - "Tier 2 neutralization was restricted to pseudoviruses matching the engineered Env-immunogen, with no cross-neutralization of parental Env-variants. Our findings support the use of VSV-GP as a potent platform for displaying native-like Env-trimers and highlight its potential in prime-boost strategies for HIV vaccine development."

Journal • Preclinical • Human Immunodeficiency Virus • Infectious Disease

Newly identified oncolytic VSV-GP-specific CD8+ T cell epitopes for monitoring of anti-viral immune responses in the BALB/c mouse model. (PubMed, Mol Ther Oncol) - "Taken together, the 11 newly identified epitopes facilitate the monitoring of anti-viral CD8+ T cells, which will aid the preclinical development of novel VSV-GP variants. This epitope-specific monitoring also serves as proof of concept for the potential future application of anti-viral immunomonitoring in clinical trial settings."

Journal • Preclinical • Oncology • CD8

The Emerging Role of Oncolytic Virotherapy in Glioblastoma Management. (PubMed, Cancers (Basel)) - "Despite maximal resection, radiotherapy, and temozolomide, median survival is still 12-15 months because of tumor heterogeneity, diffuse infiltration, and therapeutic resistance...Several viral backbones have advanced to clinical testing, including adenovirus (DNX-2401), herpes simplex virus (G47Δ, G207), poliovirus (PVS-RIPO), measles virus (MV-CEA), reovirus (pelareorep), vaccinia virus (Pexa-Vec), and vesicular stomatitis virus (VSV-GP)...Advances in delivery, such as convection-enhanced infusion and blood-brain barrier modulation, are also under investigation. Despite obstacles, oncolytic virotherapy holds significant potential within multimodal GBM strategies."

Journal • Review • Brain Cancer • Glioblastoma • Glioma • Herpes Simplex • High Grade Glioma • Infectious Disease • Measles • Oncology • Solid Tumor

Latest insights into oncolytic viro-immunotherapy with vesicular stomatitis virus. (PubMed, Semin Immunol) - "To mitigate neurotoxicity and improve therapeutic efficacy, genetically-engineered strains, such as VSV-∆M51, VSV-mIFNβ, and VSV-GP, have been developed...Ongoing research continues to explore strategies for improving systemic delivery, minimizing off-target effects, and enhancing viral persistence within the tumor bed. Further investigation and clinical translation will determine the full potential of VSV-based viroimmunotherapy in cancer treatment."

Journal • Review • Oncology • IFNB1

A Study to Test How Well Different Doses of BI 1831169 in Combination With an Anti-PD1 Antibody Are Tolerated in Japanese People With Different Advanced Cancers (clinicaltrials.gov) - P1 | N=46 | Not yet recruiting | Sponsor: Boehringer Ingelheim

New P1 trial • Oncology • Solid Tumor

Interleukin-12 encoded by the oncolytic virus VSV-GP enhances therapeutic antitumor efficacy by inducing CD8+ T-cell responses with a long-lived effector cell phenotype. (PubMed, J Immunother Cancer) - "Taken together, we have demonstrated that oncolytic virotherapy using VSV-GP encoding IL-12 induces CD8+ T cell responses characterized by an LLEC phenotype, a cell population that is likely a crucial component of antitumor immunity."

Journal • CNS Disorders • Infectious Disease • Oncology • CD8 • IFNA1 • IL12A

Tailoring the Methods of Conjugation and Characterization for a Replication-Competent, Live, Viral Vector. (PubMed, Bioconjug Chem) - "Herein, we present a comprehensive series of steps for conjugation, purification, and characterization that are adapted from traditional biologics (e.g., monoclonal antibodies) and apply them to the replication-competent rhabdovirus VSV-GP-GFP. By confirming purity and quantifying the average degree of labeling (DoL), we tailored the label/particle ratio to generate tool viruses suitable for downstream applications in nonclinical and clinical development. These methods will enhance the development of viral vector therapies and hasten their delivery to patients in need."

Journal

Perfusion process with tangential flow filtration for oncolytic VSV-GP production. (PubMed, Front Bioeng Biotechnol) - "By optimizing the perfusion process, the titer reached up to 5.1 × 1010 TCID50 mL-1, which is 17-fold higher than in batch cultivation. Overall, this work presents perfusion cultivation as an efficient technology to improve the VSV-GP titer with virus retention."

Journal • Dental Disorders • Infectious Disease • Oncology • Stomatitis

1456-0001 study: A Study to Test Different Doses of BI 1831169 Alone and in Combination With an Anti-PD-1 Antibody in People With Different Types of Advanced Cancer (Solid Tumors) (clinicaltrials.gov) - P1 | N=190 | Recruiting | Sponsor: Boehringer Ingelheim | Trial primary completion date: May 2027 ➔ Dec 2027

Monotherapy • Trial primary completion date • Oncology • Solid Tumor

1456-0001 study: A Study to Test Different Doses of BI 1831169 Alone and in Combination With an Anti-PD-1 Antibody in People With Different Types of Advanced Cancer (Solid Tumors) (clinicaltrials.gov) - P1 | N=190 | Recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: May 2028 ➔ Oct 2028

Trial completion date • Oncology • Solid Tumor

Characterization of VSV-GP morphology by cryo-EM imaging and SEC-MALS. (PubMed, Mol Ther Methods Clin Dev) - "In developing an orthogonal method with higher throughput, we showed that the morphological profile of the VSV-GP particles can be characterized by size exclusion chromatography coupled with a multi-angle light scattering detector (SEC-MALS) based on a novel shape-based separation mechanism. Together, the two complementary techniques enable the analysis of morphological profile for VSV-GP and potentially other non-spherical viruses or nanoparticles."

Journal • CNS Disorders • Infectious Disease • Oncology

Molecular Pathology Methods to Characterize Biodistribution and Pharmacodynamics of the Oncolytic Virus VSV-GP in a Nonclinical Tumor Model. (PubMed, Toxicol Pathol) - "We identified distinct patterns of viral biodistribution and replication across tumor and nontumor sites but no major differences in biodistribution, off-tumor cell tropism, or immune cell responses between tumor-free and tumor-bearing mouse models. Our findings characterize key cellular changes following systemic exposure to VSV-GP, provide a better understanding of a nonclinical permissive tumor model for OV assessment, and demonstrate how current molecular pathology methods can provide a bridge between traditional biodistribution and pathology readouts."

Journal • PK/PD data • Preclinical • CNS Disorders • Infectious Disease • Oncology • IFNAR1

Repeated harvest enables efficient production of VSV-GP. (PubMed, Front Bioeng Biotechnol) - "While no effect on cell density was observed, the cumulated infectious titer following repeated harvest was over 400 times higher than the evaluated batch process yield. This shows that repeated harvests or perfusion have the potential to boost viral yields and should be considered when deciding on a process format for production."

Journal

DEVELOPMENT OF A THERAPEUTIC HPV16 VACCINE BASED ON THE VIRAL VECTOR VSV-GP (IPVC 2024) - "Our results show that at least one local application seemed to be beneficial for induction of HPV-specific TRMS in the genital tract, which are associated with the efficacy of therapeutic HPV vaccines. To overcome the vector immunity we will further analyze heterologous prime/boost vaccination regimens. For now, taken together, VSV-GP is a promising candidate as therapeutic HPV vaccine as the vector combines a favorable safety profile with a robust induction of HPV-specific T cell responses at an entry side of HPV."

Viral vector • Human Papillomavirus Infection • Infectious Disease • Oncology

First results for intravenous (IV) VSV-GP (BI 1831169) in patients (pts) with advanced solid tumors from the 1456-0001 study (ESMO 2024) - P1 | "Here we present the first results for the IV administration of the VSV-GP in pts with advanced solid tumors. The 1456-0001 study (NCT05155332) is a Phase I, open-label, dose-escalation study evaluating intratumoral (IT), IV, or IT+IV VSV-GP as monotherapy (Part 1) or in combination with the anti-PD-1 antibody ezabenlimab (Part 2). The study is ongoing to determine the MTD of IV VSV-GP monotherapy."

Clinical • Metastases • Oncology • Solid Tumor

Updated results from the phase I 1456-0001 study for intratumoral (IT) VSV-GP (BI 1831169) in patients with advanced solid tumors (ESMO 2024) - P1 | "Here we report updated results for IT VSV-GP monotherapy. In this Phase I, open-label, dose-escalation study, VSV-GP is administered IT, intravenously (IV), or IT+IV as monotherapy (Part 1) or with the anti-PD-1 antibody ezabenlimab (Part 2). The study is ongoing to evaluate safety and determine the MTD of IT VSV-GP monotherapy."

Clinical • Metastases • P1 data • Oncology • Solid Tumor