CStone Announces Major Clinical Validation Milestone for CS2009 at ESMO 2026: Data from More Than 300 Patients Support Mechanism, Safety and Broad Antitumor Activity

October 25, 2026 — CStone Pharmaceuticals announced a major clinical validation milestone for CS2009, its investigational PD-1/VEGF/CTLA-4 trispecific antibody, following two Rapid Oral presentations at the European Society for Medical Oncology (ESMO) Congress 2026.

Highlights

• Three pillars of clinical validation: Clinical data from over 300 patients support proof of mechanism, proof of safety and proof of concept across multiple solid tumor types.

• Innovative design and triple-pathway synergy: Pharmacodynamic (PD) observations support engagement of PD-1, CTLA-4 and VEGF pathways, reinforcing the scientific rationale for CS2009’s differentiated molecular design.

• Differentiated safety profile: The growing clinical dataset shows consistent tolerability, with low rates of severe CTLA-4-associated and VEGF-related toxicities, supporting the potential for sustained treatment and combination with other therapies.

• Compelling efficacy across first-line and heavily pretreated NSCLC: CS2009 monotherapy achieved an ORR of 87.5% in first-line PD-L1-high NSCLC, reaching 100% at 30 mg/kg. In heavily pretreated NSCLC, including patients previously exposed to immunotherapy, CS2009 monotherapy demonstrated an ORR of 28.0% at 30 mg/kg, with a median duration of response of 10.5 months. In combination with chemotherapy, CS2009 achieved an ORR of 85.7% at 30 mg/kg in first-line squamous NSCLC and 55.6% at 30 mg/kg in second- or third-line immunotherapy-pretreated NSCLC.

• Strong antitumor activity in first-line and heavily pretreated pMMR/MSS metastatic colorectal cancer (mCRC): CS2009 combined with XELOX achieved an ORR of 63.6% and a DCR of 100% in first-line mCRC, including an ORR of 68.8% among patients with liver metastases. Given the limited follow-up to date, the ORR may increase as additional data mature. Importantly, CS2009 monotherapy demonstrated an ORR of 20.0% and a DCR of 93.3% in heavily pretreated mCRC, providing encouraging evidence of single-agent activity in traditionally immunotherapy-resistant pMMR/MSS disease.

• Promising antitumor activity across a broad range of additional solid tumors: Beyond NSCLC and mCRC, CS2009 has also demonstrated encouraging antitumor activity in multiple other solid tumors, including soft tissue sarcoma (STS), non-clear-cell renal cell carcinoma (nccRCC), small-cell lung cancer (SCLC), ovarian cancer, hepatocellular carcinoma, gastric cancer, esophageal cancer, metastatic castration-resistant prostate cancer (mCRPC), and triple-negative breast cancer (TNBC), further reinforcing its broad therapeutic potential as a next-generation immuno-oncology backbone.

• Global development and partnership: CStone is preparing global registrational Phase III studies and actively pursuing strategic partnership discussions with multinational pharmaceutical companies.

With clinical data generated from more than 300 patients across multiple solid tumor types, CS2009 has achieved three important clinical validation milestones: proof of mechanism, proof of safety, and proof of concept across a broad range of cancers. The latest ESMO data in NSCLC and mCRC further strengthen these validations with compelling monotherapy and combination efficacy results, including in patients previously treated with immunotherapy and those with traditionally immunologically “cold” tumors.

The results mark a significant clinical de-risking milestone and support the potential of CS2009’s innovative design to address limitations of existing immuno-oncology therapies.

Dr. Jason Yang, Chief Executive Officer, President of R&D and Executive Director of CStone, commented: “The ESMO 2026 data represent a defining milestone in the development of CS2009. In less than two years since entering clinical development, we have generated data from more than 300 patients and built compelling, converging evidence across three essential dimensions: mechanism of action, safety and antitumor efficacy across multiple cancer types. This is far more than an incremental clinical data update. We believe it is a major step in validating the scientific rationale, differentiated design and broad therapeutic potential of CS2009.

Our ambition was never simply to combine three established targets into one molecule. We designed CS2009 to integrate the complementary benefits of PD-1, VEGF and CTLA-4 blockade while addressing the systemic toxicity that has historically constrained CTLA-4-based treatment. We have now generated robust clinical data to validate this design.

We are particularly encouraged by the promising monotherapy antitumor activity observed in heavily pretreated NSCLC following prior immunotherapy, and in traditionally “cold” tumors such as mCRC. Together with the strong first-line combination results in NSCLC and mCRC, these findings underscore CS2009’s potential as a next-generation immuno-oncology backbone. We are preparing global Phase III registrational clinical trials and are in active discussions with potential multinational partners to accelerate CS2009’s development worldwide.”

Three Pillars of Clinical Validation

1. Proof of Mechanism: Target Engagement and Synergistic Activity Confirmed Across All Three Pathways

CS2009 is rationally designed to target three complementary mechanisms simultaneously. CTLA-4 blockade is intended to enhance T-cell priming and expansion, PD-1 blockade to restore the function of exhausted T cells; and VEGFA blockade to normalize tumor vasculature and counteract immunosuppression. Cooperative PD-1/CTLA-4 binding and VEGFA-driven crosslinking are designed to enhance activity within the tumor microenvironment (TME) and tumor‑draining lymph node (TDLN) while limiting CTLA-4 engagement in peripheral tissues.

Clinical PD findings include dose-dependent upregulation of inducible T-cell costimulator (ICOS) and Ki67 on CD4+ T and CD8+ T cells, sustained PD-1 and CTLA-4 receptor occupancy at doses of ≥20 mg/kg, and rapid, sustained suppression of free serum VEGFA, supporting engagement of the CTLA-4, PD-1 and VEGFA pathways. In addition, linear pharmacokinetics (PK), a half-life of approximately 6 to 9 days, and a low incidence of anti-drug antibodies (ADAs) further support clinical development. These observations are consistent with target engagement and key aspects of the intended mechanism. Definitive demonstration of clinical synergy will require further study.

2. Proof of Safety: Favorable Tolerability Across Tumor Types and Regimens

The ESMO NSCLC cohorts reported Grade ≥3 treatment-related adverse events (TRAEs) of 25.9% with monotherapy and 52.4% with chemotherapy combinations; Grade ≥3 immune-related adverse events (irAEs) of 11.6% with monotherapy and 12.7% with chemotherapy combinations; Grade ≥3 possibly VEGF-related TRAEs were 5.4% and 4.8% respectively.

In mCRC, Grade ≥3 irAEs were 13.0% with monotherapy and 21.7% with XELOX, while Grade ≥3 possibly VEGF-related TRAEs were 8.7% and 4.3%. No new safety signals were identified, and no clear additive immune-related or VEGF-related toxicity pattern was observed with chemotherapy. The safety profile in NSCLC and mCRC has remained consistent with the mature Phase I dataset, with rare incidence of severe CTLA-4-associated toxicities, such as colitis, hepatitis and skin toxicities.

These findings support that CS2009 has the potential for sustained triple-pathway inhibition with manageable tolerability.

3. Proof of Concept: Monotherapy and Combination Activity Across Multiple Tumors

Strong first-line NSCLC monotherapy efficacy

Among patients with first-line PD-L1 TPS ≥50% NSCLC, CS2009 monotherapy (30 mg/kg cohort) achieved an ORR and DCR of 100% (11/11), and the 20 mg/kg cohort achieved an ORR of 76.9% (10/13) and a DCR of 92.3% (12/13). The overall ORR and DCR in the TPS ≥50% population were 87.5% (21/24) and 95.8% (23/24), respectively.

In the broader PD-L1-positive population (TPS ≥1%), CS2009 monotherapy (30 mg/kg cohort) achieved an ORR of 75.0% (18/24) and a DCR of 91.7% (22/24), and the 20 mg/kg cohort achieved an ORR of 58.3% (14/24) and a DCR of 95.8% (23/24). The overall ORR and DCR in the TPS ≥1% population were 66.7% (32/48) and 93.8% (45/48), respectively.

Antitumor activity was consistent across histologies: among patients with TPS ≥50%, ORR was 91.7% (11/12) in squamous disease and 83.3% (10/12) in non-squamous disease; among those with TPS ≥1%, ORR was 69.0% (20/29) and 63.2% (12/19), respectively. Median PFS and DoR have not yet been reached due to limited follow-up.

Robust combination efficacy in NSCLC

In first-line squamous NSCLC, CS2009 (30 mg/kg cohort) plus paclitaxel and carboplatin achieved an ORR of 85.7% (12/14) and a DCR of 100% (14/14). The 20 mg/kg cohort achieved an ORR of 76.9% (10/13) and a DCR of 100% (13/13). The overall ORR and DCR in first-line squamous NSCLC were 81.5% (22/27) and 100% (27/27), respectively. Among these 27 patients, 22 had PD-L1 TPS ≤5%, and the ORR reached 100% (8/8) among PD-L1-negative patients (TPS <1%).

In second- or third-line NSCLC previously treated with immunotherapy and platinum-based chemotherapy, CS2009 plus docetaxel achieved an ORR of 55.6% (10/18) and a DCR of 100% (18/18) and efficacy is consistent between 20 mg/kg and 30 mg/kg groups.  

Strong combination efficacy in first-line mCRC 

In first-line pMMR/MSS metastatic colorectal cancer (mCRC), preliminary data show that CS2009 plus XELOX achieved an ORR of 63.6% (14/22) and a DCR of 100% (22/22), with an ORR of 68.8% (11/16) in patients with liver metastases and 85.7% (6/7) in those with baseline target-lesion diameters totaling more than 100mm. Given the limited follow-up to date, the ORR may increase as additional data mature.

Clinically meaningful monotherapy efficacy in difficult-to-treat populations

In heavily pretreated NSCLC, where 84.2% of patients had received prior immunotherapy, CS2009 monotherapy at 30 mg/kg achieved an ORR of 28.0% (7/25), a disease control rate (DCR) of 60.0% (15/25) and a median duration of response (mDoR) of 10.5 months; multiple patients remained on treatment for more than 12 months.

In heavily pretreated pMMR/MSS mCRC, a classical “cold tumor”, CS2009 monotherapy at 30 mg/kg achieved an ORR of 20.0% (3/15) and a DCR of 93.3% (14/15).

Encouraging activity in additional solid tumors

Beyond the key NSCLC and mCRC cohorts, CS2009 has demonstrated promising antitumor activity in additional solid tumors, including STS, nccRCC, SCLC, ovarian cancer, hepatocellular carcinoma, gastric cancer, esophageal cancer, metastatic CRPC and TNBC. These observations reinforce the potential breadth of CS2009 as an immuno-oncology backbone. Detailed data for these additional tumor types have not been publicly disclosed in the ESMO presentations.

Advancing Toward Global Registrational Development

With the accumulating clinical data, CStone plans to initiate global, multicenter, registrational Phase III trials by the end of 2026. In parallel, CStone is in active discussions with multinational pharmaceutical companies for potential partnerships aimed at accelerating global development and maximizing the therapeutic and commercial potential of CS2009.