On September 23, 2025 CStone Pharmaceuticals (stock code: 2616.HK), an innovation-driven biopharmaceutical company focused on developing therapeutics for key disease areas such as oncology, autoimmunity, and inflammation, reported that the first patient has been enrolled in a global, multi-center Phase II clinical trial of CS2009 (a PD-1/VEGF/CTLA-4 trispecific antibody) in Australia (Press release, CStone Pharmaceauticals, SEP 23, 2025, View Source [SID1234656216]). The trial is currently actively enrolling patients in Australia and China, with plans to expand to the United States in the future.
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Phase I dose-escalation study shows positive potential
In the completed Phase I study with escalation and supplemental enrollment across six dose groups (1-45 mg/kg), CS2009 demonstrated:
1. Excellent safety : No dose-limiting toxicity (DLT) was observed in all evaluated dose groups , and dozens of patients had good overall tolerance.
2. Pharmacokinetics/pharmacodynamics (PK/PD) are in line with expectations :
(1) PK characteristics support a three-week dosing schedule, with no accumulation after multiple dosing;
(2) PD data also confirmed that CS2009 achieved saturated receptor occupancy by blocking PD-1/CTLA-4, triggering T cell activation and proliferation, and had a strong and lasting neutralizing effect on VEGFA.
3. Broad and deepening anti-tumor activity :
(1) Significant anti-tumor activity was observed at all doses, and the activity continued to increase with prolonged follow-up ;
(2) Anti-tumor activity was observed in a variety of tumor types, including "cold tumors" and PD-(L)1 refractory/resistant patients;
(3) Most patients are still receiving ongoing treatment.
We will present the Phase I clinical study data of CS2009 at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Meeting in October.
Global Phase II trials deepen coverage of multiple cancer types
The global multi-center Phase II trial, which has been launched, adopts a multi-cohort parallel expansion design and will cover 15 cohorts and multiple solid tumor indications, focusing on evaluating the safety, tolerability, PK/PD characteristics and efficacy of CS2009 as a single agent and in combination therapy. Specific study cohorts include:
1. Non-small cell lung cancer (NSCLC):
Monotherapy for treatment -naive patients with PD-L1-positive (tumor proportion score [TPS] ≥ 1%) and negative targetable driver gene alterations (AGA);
First-line treatment in combination with chemotherapy for non-squamous, AGA-negative patients;
First-line treatment in combination with chemotherapy for squamous, AGA-negative patients;
Combined chemotherapy for the treatment of PD-(L)1 refractory/resistant patients who have failed first-line treatment;
Combination chemotherapy for the treatment of non-squamous patients with EGFR mutations who have failed EGFR-TKI treatment and have not been treated with chemotherapy.
2. Hepatocellular carcinoma (HCC): Monotherapy for patients with unresectable advanced HCC who have failed ≤2 lines of treatment.
3. Colorectal cancer (CRC): Combined with chemotherapy as the first-line treatment for patients with normal mismatch repair/microsatellite stable (pMMR/MSS) tumors.
4. Platinum-resistant ovarian cancer (PROC):
Patients who have failed ≤2 lines of treatment after platinum-resistant monotherapy ;
Combination chemotherapy for patients who have failed ≤2 lines of treatment.
5. Triple-negative breast cancer (TNBC):
Patients who have failed ≤2 lines of monotherapy ;
First-line treatment with combined chemotherapy .
6. Extensive-stage small cell lung cancer (ES-SCLC): first-line treatment with combined chemotherapy.
7. Cervical cancer (CC): First-line treatment with combined chemotherapy.
8. Gastric cancer or gastroesophageal junction cancer (GC/GEJC): First-line treatment with combined chemotherapy.
9. Esophageal squamous cell carcinoma (ESCC): first-line treatment with combined chemotherapy.
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 interactions 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 exhibiting comparable VEGF neutralization activity to existing anti-VEGF antibodies. It targets a broad range of diseases, including but not limited to non-small cell lung cancer, small cell lung cancer, liver cancer, gastric cancer, ovarian cancer, cervical cancer, breast cancer, esophageal cancer, and colorectal cancer.