Phase 1/2 CS2009 PD-1/VEGFA/CTLA-4 trispecific antibody in advanced solid tumors

This first-in-human, open-label, multicenter Phase 1/2 study evaluates CS2009, CStone Pharmaceuticals’ trispecific monoclonal antibody designed to block PD-1 (reinvigorates exhausted T cells), CTLA-4 (promotes T-cell priming/activation), and VEGFA (suppresses tumor angiogenesis and can normalize the tumor microenvironment). Phase 1 uses dose escalation to define safety, tolerability, pharmacokinetics, and a recommended dose; Phase 2 expands into tumor- and regimen-specific cohorts, including CS2009 monotherapy and combinations with commonly used chemotherapies such as platinum agents (carboplatin/cisplatin/oxaliplatin), taxanes (paclitaxel/docetaxel/nab-paclitaxel), pemetrexed, etoposide, and fluoropyrimidine-based regimens (5-FU/capecitabine/leucovorin). Eligible patients have advanced/metastatic, unresectable solid tumors (including settings where there is no standard option), aiming to show early anti-tumor activity and identify combination backbones that could be commercially scalable across large indications. Today, most advanced solid tumors are treated with PD-(L)1–based immunotherapy when indicated and/or histology-driven chemotherapy (often platinum doublets), with later-line targeted therapy or ADCs when biomarkers fit; CS2009’s angle is delivering “triple-pathway” IO + anti-angiogenesis in a single molecule to potentially improve efficacy while managing CTLA-4–associated toxicity seen with dual-checkpoint combinations.