CStone Pharmaceuticals has received Investigational New Drug (IND) clearance from the U.S. Food and Drug Administration (FDA) to initiate a Phase II clinical trial of its core asset, CS2009, in patients with advanced solid tumours.

The milestone marks a key step in the global clinical development of CS2009, an innovative PD-1/VEGF/CTLA-4 trispecific antibody designed to deliver synergistic anti-tumour activity. The global, multicentre Phase II trial is currently enrolling patients in Australia and China and has now secured regulatory clearance in the United States.

The study adopts a multi-cohort, parallel expansion design and includes 15 cohorts evaluating CS2009 as both monotherapy and in combination regimens across nine solid tumour indications. These include Non-Small Cell Lung Cancer (NSCLC), Colorectal Cancer (CRC), Triple-Negative Breast Cancer (TNBC), extensive-stage Small Cell Lung Cancer (ES-SCLC), Platinum-Resistant Ovarian Cancer (PROC), cervical cancer, Hepatocellular Carcinoma (HCC), Gastric or Gastroesophageal Junction Cancer (GC/GEJC) and Esophageal Squamous Cell Carcinoma (ESCC).

Initial Phase I data, presented at the 2025 European Society for Medical Oncology (ESMO) Annual Meeting, demonstrated a favorable safety profile along with encouraging antitumor activity. Additional data from both Phase I and Phase II studies are expected to be presented later this year at upcoming American Society of Clinical Oncology (ASCO) and ESMO congresses.

Dr. Jason Yang, CEO, President of R&D and Executive Director at CStone, said the FDA clearance followed productive engagement with the agency, which reviewed comprehensive Phase I safety and efficacy data from dose-escalation and expansion cohorts. He added that the agency aligned with the company on key aspects of the Phase II study design, including dose optimisation and expansion strategies, and that CStone is actively advancing the global development programme.

CS2009 is designed to target three clinically validated pathways PD-1, VEGFA and CTLA-4—through a single trispecific antibody platform. The anti-PD-1 component aims to reverse T-cell exhaustion, anti-CTLA-4 promotes T-cell activation and proliferation and anti-VEGFA inhibits tumour angiogenesis while improving the tumor microenvironment.

Within the tumour microenvironment, the PD-1 and CTLA-4 inhibitory effects are enhanced through VEGFA-mediated crosslinking. The molecule is engineered to preferentially block PD-1 and CTLA-4 on double-positive tumour-infiltrating T cells, while minimising disruption of CTLA-4 regulation in peripheral T cells.

The Phase II study is designed to evaluate efficacy, safety, tolerability and pharmacokinetics/pharmacodynamics (PK/PD) of CS2009 across the selected tumour indications. With regulatory clearance in the U.S. and active enrollment underway in Australia and China, CStone continues to position CS2009 as a potential first- or best-in-class trispecific immunotherapy candidate for advanced solid tumours.