CStone announces first patient enrollment in global Phase II trial of CS2009 (PD-1/VEGF/CTLA-4 trispecific antibody) in Australia

On September 23, 2025, CStone Pharmaceuticals ("CStone," HKEX: 2616), an innovation-driven biopharmaceutical company focused on the research and development of therapies for oncology, autoimmune/inflammation, and other key disease areas, announced that the first patient has been enrolled in Australia in the global multicenter Phase II clinical trial of core asset CS2009 (PD-1/VEGF/CTLA-4 trispecific antibody). The trial enrollment is currently ongoing in Australia and China, with subsequent expansion planned for the United States.

Phase I Dose-Escalation Study Demonstrates Promising Profile

In the Phase I dose-escalation study (6 cohorts, 1-45mg/kg, escalation and backfilling), CS2009 showed:

- Favorable Safety: No dose-limiting toxicities (DLT) observed across all evaluated doses, and well-tolerated in dozens of patients.

- PK/PD Characteristics as Expected:

·Every-three-week (Q3W) dosing supported by linear pharmacokinetic with no accumulation;

·Saturated receptor occupancy and robust T-cell activation/proliferation via PD-1/CTLA-4 blockade and potent and sustained VEGFA neutralization.

- Broad & Deepening Antitumor Activity:

·Notable anti-tumor activity was observed across all doses, and the activity continued to strengthen with prolonged follow-up;

·Activity demonstrated in multiple tumor types, including cold tumors and PD-(L)1-refractory and resistant patients;

·Most patients remain on treatment.

Phase I data will be presented at the European Society for Medical Oncology (ESMO) Congress in October 2025.

Global Phase II Trial Design Across Multiple Tumors

The multi-cohort expansion trial will evaluate CS2009 monotherapy and combination regimens across 15 cohorts covering multiple solid tumor indications:

- Non-Small Cell Lung Cancer (NSCLC):

·Monotherapy in treatment-naïve PD-L1 positive (tumor proportion score [TPS]≥1%), actionable genomic alterations (AGA) negative patients;

·Combination with chemotherapy in first-line non-squamous AGA negative patients;

·Combination with chemotherapy in first-line squamous AGA negative patients;

·Combination with chemotherapy in second-line PD-(L)1 refractory/resistant patients;

·Combination with chemotherapy for EGFR-mutant non-squamous patients after EGFR-TKI failure.

- Hepatocellular Carcinoma (HCC): Monotherapy in unresectable advanced HCC after ≤2 prior systemic therapies.

- Colorectal Cancer (CRC): Combination with chemotherapy in first-line proficient mismatch repair/microsatellite stable (pMMR/MSS) patients.

- Platinum-Resistant Ovarian Cancer (PROC):

·Monotherapy after ≤2 lines post-platinum resistance;

·Combination with chemotherapy after ≤2 prior therapies.

- Triple-Negative Breast Cancer (TNBC):

·Monotherapy after ≤2 prior therapies;

·Combination with chemotherapy in first-line setting.

- Extensive-Stage SCLC (ES-SCLC): Combination with chemotherapy as first-line treatment.

- Cervical Cancer (CC): Combination with chemotherapy as first-line treatment.

- Gastric/Gastroesophageal Junction Cancer (GC/GEJC): Combination with chemotherapy as first-line treatment.

- Esophageal Squamous Cell Carcinoma (ESCC): Combination with chemotherapy as first-line treatment.

About CS2009 (PD-1/VEGF/CTLA-4 Trispecific Antibody)

CS2009 is a novel trispecific antibody targeting PD-1, VEGFA, and CTLA-4 to achieve multidimensional antitumor effects through synergistic mechanisms. It is independently developed by CStone from molecular inception, with the potential to be first- or best-in-class. Its differentiated molecular design combines these validated targets, preferentially invigorating exhausted tumor infiltrating lymphocytes (TILs) while demonstrating VEGF neutralization comparable to existing anti-VEGF antibodies. CS2009 covers a wide range of cancers, including but not limited to non-small cell lung cancer, small cell lung cancer, hepatocellular carcinoma, gastric cancer, ovarian cancer, cervical cancer, breast cancer, colorectal cancer, esophageal cancer etc.

About CStone

CStone (HKEX: 2616), established in late 2015, is an innovation-driven biopharmaceutical company focused on the research and development of therapies for oncology, autoimmune/inflammation, and other key disease areas. Dedicated to addressing patients' unmet medical needs in China and globally, the Company has made significant strides since its inception. To date, the Company has successfully launched 4 innovative drugs and secured approvals for 16 new drug applications covering 9 indications. The company's pipeline is balanced by 16 promising candidates, featuring potentially first-in-class or best-in-class antibody-drug conjugates (ADCs), multispecific antibodies, immunotherapies and precision medicines. CStone also prides itself on a management team with comprehensive experiences and capabilities that span the entire drug development spectrum, from preclinical and translational research to clinical development, drug manufacturing, business development, and commercialization.

Source: CStone