#China #Suzhou #oncology #CStone Pharmaceuticals #CS2009

CStone Pharmaceuticals Unveils Groundbreaking Phase I Results for Trispecific Antibody CS2009 at ESMO 2025

CStone Pharmaceuticals, a pioneering biopharmaceutical company based in Suzhou, China, recently made headlines at the 2025 European Society for Medical Oncology (ESMO) Annual Congress by presenting its preliminary Phase I data for CS2009, a novel PD-1/VEGF/CTLA-4 trispecific antibody. This marks a significant development in the field of oncology, as it represents the first-ever clinical data publication for a trispecific antibody targeting these three critical pathways in cancer treatment.

Overview of CS2009 Development

This phase I study, known as CS2009-101, is currently being conducted across multiple regions including Australia and China, focusing on assessing the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and anti-tumor efficacy of CS2009 in patients suffering from advanced solid tumors. The study aims to provide vital insights into the antibody's potential as a therapeutic option in the competitive oncology landscape.

As of the defined data cutoff, a total of 72 patients were enrolled across six dose levels (ranging from 1 to 45 mg/kg), with 72.2% of participants still continuing their treatment. Many patients had previously received various immuno-oncology therapies, highlighting the challenge of developing effective treatments for heavily pretreated populations.

Safety and Tolerability

Remarkably, the dose escalation phase of this trial has concluded without any reports of dose-limiting toxicity. The team did not observe any Grade 4 or 5 treatment-related adverse events, and the incidence of Grade ≥3 treatment-related adverse events (TRAEs), immune-related adverse events (irAEs), and VEGF-related TRAEs stood at 13.9%, 4.2%, and 2.8%, respectively. Only one treatment-emergent adverse event led to permanent discontinuation, evidencing the agent's favorable safety profile.

Antitumor Activity Results

While long-term follow-up data remain limited, interim results reveal promising antitumor activity across diverse solid tumors. After the cutoff period, 49 out of the 72 patients underwent post-baseline tumor assessments. The overall response rate (ORR) recorded at this stage was 12.2%, with a disease control rate (DCR) of 71.4%. Excitingly, as follow-up progresses, the ORR has shown an upward trend, reaching 14.3% overall. The best response was noted at the recommended Phase 2 dose (RP2D) of 30 mg/kg, where the ORR climbed to an impressive 25.0%.

Specific responses in various tumor types included:

• - Non-Small Cell Lung Cancer (NSCLC): ORR 11.8%, DCR 82.4%. With further updates post-ESMO, the ORR increased to 17.6%.
• - Ovarian Cancer (OC): ORR 16.7%, DCR 66.7%.
• - Triple-Negative Breast Cancer (TNBC): ORR 25.0%, DCR 75.0%.
• - Non–Clear Cell Renal Cell Carcinoma (nccRCC): ORR 33.3%, DCR 100%.
• - Soft Tissue Sarcoma (STS): ORR 11.1%, DCR 66.7%.

These preliminary results underscore CS2009's potential effectiveness across multiple oncological indications, which may lead to promising treatment avenues for patients facing limited options.

Pharmacokinetic and Pharmacodynamic Profiles

Pharmacokinetic analysis indicates a linear profile for CS2009 with a half-life of 6-8 days, supporting a dosing regimen every three weeks. The PD profile confirms notable receptor saturation and robust T-cell activation in peripheral T cells, showcasing the antibody's efficacy at PD-1 and CTLA-4 inhibition.

Moreover, serum-free VEGFA levels were significantly reduced across all dosage levels, maintaining this reduction throughout the dosing intervals, indicating a sustained therapeutic effect.

Next Steps and Future Expectations

In light of these findings, CStone has announced the initiation of a Phase II dose expansion study, targeting first-line treatment in patients with various tumor types. The aim is to optimize dosage and gather data necessary for supporting registration trials for CS2009 in both monotherapy and combination therapy settings.

CStone will be hosting a conference call to discuss these results and future strategies with investors. Both Chinese and English sessions are scheduled for October 20, 2025, offering insights into the company’s plans in further clinical developments.

For those interested in CStone's progress and innovations in biopharmaceuticals, further updates can be expected as the company continues to prioritize the needs of patients worldwide. As it stands, CStone showcases its commitment to advancing cancer therapies through innovative research and dedication to addressing unmet medical needs.