CStone Pharmaceuticals-B (02616) has announced the latest clinical progress for its internally developed PD-1/VEGF/CTLA-4 trispecific antibody, CS2009. The data demonstrate an excellent safety profile: as of mid-March 2026, the Phase I trial had enrolled 113 patients with advanced solid tumors. With a median follow-up of approximately six months, increasingly mature data continue to confirm its outstanding safety characteristics. The incidence of Grade 3 or higher treatment-related adverse events (TRAEs) was 23%. Furthermore, no severe toxicities typically frequent in combination therapies containing CTLA-4 and PD-(L)1 inhibitors were observed, and the incidence of Grade 3 or higher VEGF-related adverse events was low.

The therapy has shown robust efficacy in lung cancer. Preliminary Phase I/II efficacy data for CS2009 monotherapy in lung cancer are positive. Among first-line non-small cell lung cancer (NSCLC) patients with a PD-L1 Tumor Proportion Score (TPS) of ≥50%, the objective response rate (ORR) reached 90%, and the disease control rate (DCR) was 100%. In second-line and later-line NSCLC patients who were previously treated with immunotherapy (IO) and were negative for actionable driver genes (AGA), the ORR was 25%.

CS2009 demonstrates broad-spectrum anti-tumor potential, including activity against "cold tumors." The monotherapy also exhibited potent anti-tumor activity in later-line "cold tumor" patients who are insensitive to PD-(L)1 monoclonal antibodies. In patients with non-clear cell renal cell carcinoma (nccRCC), the ORR reached 40%, and in patients with soft tissue sarcoma (STS), the ORR was 33.3%, highlighting its potential for treating various tumor types.

The company is accelerating its global Phase III development plan. CStone Pharmaceuticals plans to initiate the first batch of global Phase III multi-regional clinical trials (MRCTs) for CS2009 by the end of 2026, focusing on indications such as NSCLC, colorectal cancer (CRC), and small cell lung cancer (SCLC).

Regarding data release plans, more Phase I and Phase II clinical research data for CS2009 are expected to be presented in 2026 at the American Society of Clinical Oncology (ASCO) Annual Meeting and/or the European Society for Medical Oncology (ESMO) Congress.

Patient enrollment is progressing rapidly, with Phase I/II data confirming excellent safety and efficacy. The global multi-center Phase I/II clinical trial for CS2009 is rapidly accumulating clinical data in Australia and China. Its Investigational New Drug (IND) application for Phase II trials has also been approved by the U.S. Food and Drug Administration (FDA). By mid-March 2026, the Phase I study had enrolled a total of 113 patients with advanced solid tumors, with a median follow-up of about six months; the Phase II study had enrolled a total of 85 patients.

Phase I data further validate the excellent safety of CS2009. Across all six evaluated dose levels, CS2009 demonstrated a favorable safety profile and tolerability. No dose-limiting toxicities (DLTs) occurred, and the maximum tolerated dose (MTD) was not reached. The incidence of Grade 3 or higher TRAEs was 23%; the incidence of Grade 3 or higher immune-related adverse events (irAEs) was 12.4%; and the incidence of Grade 3 or higher VEGF-related TRAEs was 4.4%. Severe toxicities commonly seen in CTLA-4 and PD-(L)1 combination regimens were not observed.

The therapy demonstrates broad-spectrum anti-tumor activity in IO-pretreated tumors and "cold tumors." Anti-tumor activity for CS2009 was observed across all dose groups and showed potent efficacy in multiple tumor types. At the 30mg/kg, Q3W dose level, CS2009 monotherapy in IO-pretreated, AGA-negative second-line and later-line NSCLC patients resulted in an ORR of 25% (6/24) and a DCR of 58.3% (14/24). At various dose levels, CS2009 monotherapy achieved an ORR of 40% and a DCR of 100% in "cold tumor" nccRCC patients (n=5). At various dose levels, CS2009 monotherapy achieved an ORR of 33.3% and a DCR of 66.7% in "cold tumor" STS patients (n=9).

Early Phase II trial data show promise, demonstrating potentially transformative efficacy and good tolerability when combined with standard chemotherapy in first-line NSCLC and first-line CRC. The global multi-center Phase II clinical trial for CS2009 employs a multi-cohort parallel expansion study design. It aims to evaluate the efficacy and safety of CS2009 both as a monotherapy and in combination therapies across 15 cohorts involving nine solid tumor indications. These indications include NSCLC, colorectal cancer (CRC), extensive-stage small cell lung cancer (ES-SCLC), cervical cancer (CC), gastric or gastroesophageal junction cancer (GC/GEJC), esophageal squamous cell carcinoma (ESCC), platinum-resistant ovarian cancer (PROC), triple-negative breast cancer (TNBC), and hepatocellular carcinoma (HCC).

Monotherapy shows impressive efficacy in first-line NSCLC. CS2009 monotherapy (20 mg/30 mg, Q3W) in first-line NSCLC patients with PD-L1 TPS ≥50% (n=9 evaluable for ORR in a cohort of 10) achieved an ORR of 90% (9/10) and a DCR of 100% (10/10).

Combination therapy demonstrates good tolerability and promising efficacy. Safety data from multiple CS2009 plus standard chemotherapy cohorts indicate that the combination therapy is well-tolerated across various tumor types, including first-line lung cancer and first-line colorectal cancer. It did not increase the incidence or severity of chemotherapy-related adverse events, and preliminary efficacy data are significant.

CStone has a clear and efficient global clinical development strategy for CS2009. The company plans to initiate the first batch of Phase III MRCTs for CS2009 by the end of 2026, focusing on indications such as NSCLC, CRC, and SCLC. More Phase I and II clinical research data for CS2009 are expected to be presented in 2026 at the ASCO Annual Meeting and/or the ESMO Congress.

CS2009 is a novel trispecific antibody wholly discovered and developed by CStone Pharmaceuticals from the molecular design stage, possessing first-in-class (FIC) and best-in-class (BIC) potential. It targets three clinically validated targets—PD-1, VEGFA, and CTLA-4—achieving multi-dimensional anti-tumor effects through synergistic action. Specifically, blocking PD-1 can reverse T-cell exhaustion, blocking CTLA-4 can promote T-cell activation and proliferation, and blocking VEGFA can inhibit tumor angiogenesis, thereby improving the tumor microenvironment (TME). Within the TME, the dual blockade of PD-1 and CTLA-4 is significantly enhanced through cross-linking with VEGFA. Additionally, CS2009 is designed to preferentially bind to tumor-infiltrating T cells that are positive for both PD-1 and CTLA-4, while minimizing disruption to the CTLA-4 regulatory pathway in peripheral T cells.