On July 7, 2025 CStone Pharmaceuticals (stock code: 2616.HK), an innovation-driven biopharmaceutical company focused on the research and development of anti-cancer drugs, reported the latest clinical progress of CS2009 (a trispecific antibody targeting PD-1/VEGF/CTLA-4) (Press release, CStone Pharmaceauticals, JUL 7, 2025, View Source [SID1234656218]).

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CS2009 is a potential first-in-class/best-in-class PD-1/VEGF/CTLA-4 trispecific antibody independently developed by CStone Pharmaceuticals. It possesses balanced monovalent PD-1 and CTLA-4 binding arms and a bivalent VEGFA binding arm, resulting in potent multi-target synergy and preferential tumor targeting to minimize systemic toxicity.

CS2009 uses affinity-driven target binding to preferentially block PD-1 and CTLA-4 on PD-1/CTLA-4 double-positive tumor-infiltrating T cells, while minimizing interference with the CTLA-4 signaling pathway on peripheral T cells. This is expected to improve efficacy while reducing systemic toxicity. Within the tumor microenvironment (TME), crosslinking with upregulated VEGFA dimers within the TME significantly enhances CS2209’s anti-PD-1 and anti-CTLA-4 activities.

Key Highlights:

The CS2009 global, multicenter Phase I/II clinical study is actively recruiting patients in Australia and China, with plans to expand to the United States for Phase II enrollment. Driven by strong interest from researchers and patients, the trial is rapidly enrolling, and the number of patients is expected to exceed 100 by the end of the year.
A Phase Ia dose-escalation study has completed four dose levels in patients with previously treated advanced solid tumors. The fourth dose level (20 mg/kg, administered every three weeks) was free of dose-limiting toxicities (DLTs) as assessed by the Safety Monitoring Committee (SMC) . The study is currently enrolling patients at the fifth dose level (30 mg/kg, administered every three weeks). The primary objective of the study is to investigate the safety of CS2009 above the potential recommended Phase II dose (RP2D) and to expand its safety margin. The study is also continuing with backfilling of the previous dose cohorts (1 to 20 mg/kg, administered every three weeks). A Phase Ib/Phase II dose-expansion/pivotal extension study is expected to initiate in the second half of 2025.
To date, CS2009 has demonstrated good tolerability at all evaluated dose levels, with excellent pharmacokinetic (PK) characteristics supporting a once-three-week dosing regimen. Pharmacodynamic (PD) data also confirm that CS2209-triggered PD-1/CTLA-4 blockade activates T cells and neutralizes VEGFA, and anti-tumor activity has been observed in low-dose groups of "cold tumors" and PD-(L)1-treated patients.
Phase Ia clinical data (including safety, PK, PD and anti-tumor activity) are expected to be released at an international academic conference in the fourth quarter of 2025.

CS2009 global multi-center clinical trial

The Phase I study of CS2009 is a global, multicenter clinical trial. The Phase Ia study involves dose escalation and supplemental enrollment, aiming to evaluate the safety, tolerability, PK, and anti-tumor activity of CS2009 in patients with advanced solid tumors. The Phase Ib/Phase II study is a dose expansion and pivotal study extension, exploring the safety, tolerability, PK, and efficacy of CS2009 as a single agent and in combination in various solid tumors using multiple parallel cohorts.

The trial will deeply evaluate the clinical application value of CS2009 in a variety of advanced solid tumors, including but not limited to non-small cell lung cancer, liver cancer, gastric cancer, endometrial cancer, ovarian cancer, renal cell carcinoma, colorectal cancer and cervical cancer , aiming to promote the development of innovative tumor immunotherapy.

About CS2009 (PD-1/VEGF/CTLA-4 trispecific antibody)

CS2009 is a novel trispecific antibody targeting PD-1, VEGFA, and CTLA-4, independently developed by CStone Pharmaceuticals from the molecular design perspective. It achieves multi-dimensional anti-tumor effects through synergistic action and holds first-in-class/best-in-class potential. CS2009’s differentiated molecular design combines three clinically validated targets, enabling the reactivation of near-exhausted tumor-infiltrating T cells and demonstrating comparable VEGF neutralization to existing anti-VEGF antibodies. It targets a broad range of diseases, including but not limited to non-small cell lung cancer, liver cancer, gastric cancer, endometrial cancer, ovarian cancer, renal cell carcinoma, and cervical cancer.