Undisclosed anti-PD-1×CTLA-4×VEGF TsAb / Jiangsu Hengrui Pharma - LARVOL DELTA

A novel anti-PD-1×CTLA-4×VEGF tri-specific antibody enables tumor-selective immune checkpoint blockade with potent anti-tumor activity (AACR 2026) - "In the MC38 syngeneic mouse model, the tri-specific antibody produced superior tumor growth inhibition relative to pembrolizumab or ipilimumab monotherapy, indicating cooperative immune checkpoint engagement. In the COLO205 xenograft model, anti-tumor activity was comparable to bevacizumab, confirming preserved VEGF pathway blockade and anti-angiogenic function.Moreover, non-human primate studies demonstrated favorable tolerability, pharmacokinetic behavior, and developability characteristics of the tri-specific antibodies, with no unexpected safety findings, supporting further translational development.In summary, this novel PD-1 × CTLA-4 × VEGF tri-specific antibody integrates immune checkpoint inhibition with angiogenesis blockade through a rationally designed, avidity-based mechanism that conditionally enhances CTLA-4 engagement in tumor-relevant immune contexts. These preclinical findings support its potential as a next-generation immuno-oncology therapy..."

Checkpoint block • Checkpoint inhibition • Late-breaking abstract • Trispecific • Oncology • IL2

A novel trispecific antibody HC010 targeting PD-1/CTLA-4/VEGF for the potential treatment in anti-PD-1 antibody resistant NSCLC patients (AACR 2024) - "Pembrolizumab, sintilimab and a Standard of Care (SoC) agent docetaxel were included as reference. Our trispecific antibody HC010 targeting PD-1/CTLA-4/VEGF showed a superior anti-tumor effect in a sintilimab resistant PDX animal model when compared with pembrolizumab and sintilimab as well as SoC. By analyzing tumor microenvironment , HC010 overcame acquired resistance by modulating tumor microenvironment such as increase in intra-tumoral cytotoxic T cell infiltration and normalization of blood vessels. Together with preclinical efficacy and safety data, HC010 showed potential benefits in treatment of anti-PD-1 antibody resistant NSCLC patients."

Clinical • IO biomarker • Trispecific • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD31 • CD8 • PECAM1

Development of GB268, a tri-specific antibody targeting PD-1/CTLA-4/VEGF, with enhanced anti-tumor efficacy and reduced toxicity in pre-clinical studies (AACR 2024) - "Combined application of bevacizumab and PD-1/PD-L1 blockade displays durable and improved anti-tumor effects...In arthritis induction model using hPD1/hCTLA4 double KI mice, GB268 had improved tolerance than cadonilimab and at least 20-fold better safety profile than ipilimumab combined with nivolumab. GB268 is a first-in-class anti-PD-1/CTLA-4/VEGF tri-specific antibody with innovative design... GB268 is a first-in-class anti-PD-1/CTLA-4/VEGF tri-specific antibody with innovative design. Preclinical data demonstrated GB268 is very effective in provoking anti-tumor responses. At the meantime, immune-related AEs is alleviated."

IO biomarker • Preclinical • Trispecific • Cervical Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD80 • CD86