FDA Clears Phase II Study of CStone’s PD-1/VEGF/CTLA-4 Trispecific Antibody

China-based CStone Pharmaceuticals (CStone) has received FDA clearance of its investigational new drug (IND) application for CS2009, a trispecific antibody targeting programmed cell death protein 1 (PD-1), vascular endothelial growth factor (VEGF), and cytotoxic T lymphocyte associated antigen 4 (CTLA-4). The clearance enables the program to advance into a global Phase II clinical trial in patients with advanced solid tumors, marking a regulatory milestone for the company’s multispecific immuno-oncology portfolio.¹

The ongoing multicenter Phase II study is actively enrolling patients in Australia and China and is designed to evaluate CS2009 as both monotherapy and in combination regimens. The trial includes 15 cohorts across nine solid tumor indications, including non-small cell lung cancer, colorectal cancer, triple-negative breast cancer, extensive-stage small cell lung cancer, platinum-resistant ovarian cancer, cervical cancer, hepatocellular carcinoma, gastric or gastroesophageal junction cancer, and esophageal squamous cell carcinoma.

Initial Phase I data, which the company previously presented at the 2025 European Society for Medical Oncology annual meeting, demonstrated a favorable safety profile with encouraging antitumor activity during dose-escalation and expansion phases. Additional data from Phase I and ongoing Phase II cohorts are expected to be presented at upcoming American Society of Clinical Oncology and European Society for Medical Oncology meetings later in 2026.¹

What differentiates CS2009’s trispecific immunotherapy design?

CS2009 is engineered to simultaneously engage three clinically validated immuno-oncology targets: PD-1, VEGFA, and CTLA-4. The molecule is designed to deliver coordinated immune checkpoint inhibition while modulating the tumor microenvironment.

Mechanistically, PD-1 blockade is intended to reverse T cell exhaustion, CTLA-4 inhibition promotes T cell activation and proliferation, and VEGFA targeting suppresses tumor angiogenesis while potentially improving immune cell infiltration within the tumor microenvironment.² According to the company, crosslinking with VEGFA enhances checkpoint inhibition activity within tumors, while preferential targeting of PD-1 and CTLA-4 on double-positive tumor-infiltrating T cells may reduce peripheral immune interference.¹

This multi-target strategy aims to consolidate mechanisms typically addressed through combination regimens into a single biologic construct, potentially optimizing pharmacodynamic synergy and simplifying clinical development pathways.³

How is the global Phase II study structured?

According to the company, the Phase II trial follows a multi-cohort, parallel expansion design to evaluate efficacy, safety, tolerability, and pharmacokinetics/pharmacodynamics across tumor types. Both monotherapy and combination therapy cohorts are included, allowing assessment of dose optimization and tumor-specific activity.

“We are pleased to receive FDA clearance to proceed with the global Phase II clinical trial of CS2009,” said Jason Yang, MD, PhD, CEO, president of R&D, and executive Director, CStone, in a company press release.¹ “This milestone follows a productive interaction with the agency, during which they reviewed our comprehensive Phase I data—including safety and antitumor activity data collected during dose escalation and expansion—and provided alignment on key elements of the Phase II study design, including dose optimization and expansion strategies. We are now actively advancing CS2009 clinical program globally and look forward to sharing further updates as the study progresses.”

The IND clearance in the United States expands the geographic scope of the CS2009 program, positioning the candidate within a broader regulatory framework as CStone advances global clinical development.

CStone’s oncology pipeline includes antibody-drug conjugates, multispecific antibodies, and precision therapies. The advancement of CS2009 into Phase II falls in line with the company’s ongoing investment in next-generation immunotherapy platforms aimed at addressing unmet needs across multiple solid tumor indications.¹

References

1. CStone Pharmaceuticals. CStone Announces FDA Clearance of IND Application for Its Novel Trispecific Antibody CS2009 (PD-1/VEGF/CTLA-4) to Advance into Phase II Clinical Trial. Press Release. Feb. 16, 2026.
2. Iwamoto H, Koga H, Kawaguchi T. Distinct tumor immune microenvironment modulation by anti–PD-1/PD-L1, VEGF, and CTLA-4 blockade provides a rationale for triplet therapy in hepatocellular carcinoma. Clin Mol Hepatol. 2026;32(1):e38-e42. doi:10.3350/cmh.2025.0983
3. Elshiaty M, Schindler H, Christopoulos P. Principles and Current Clinical Landscape of Multispecific Antibodies against Cancer. Int J Mol Sci. 2021;22(11):5632. doi: 10.3390/ijms22115632