CSPC Pharmaceutical Group (HKEX: 1093) has initiated a first-in-human Phase I clinical trial of SYS6051, a tissue factor (TF)-targeting antibody-drug conjugate carrying an exatecan payload, in patients with advanced solid tumors. CSPC's molecule enters a target class that already has one approved agent but where payload-related toxicity remains a clinical constraint.
The Phase I study (NCT07591285) enrolls up to 114 adults with histologically or cytologically confirmed advanced solid tumors, an ECOG performance status of 0 or 1, and at least one RECIST 1.1-measurable lesion. The study opened in May 2026 and is structured in two sequential parts: a dose-escalation and backfill phase to establish the maximum tolerated dose and recommended Phase II dose, followed by expansion cohorts. SYS6051 is administered by intravenous infusion every three weeks, with weight-based dosing calculated at screening and before each subsequent cycle. Primary completion is expected by May 2028, according to the trial record.
Primary endpoints cover the safety and tolerability profile — adverse event frequency and severity, dose-limiting toxicities — alongside the recommended Phase II dose and overall response rate. Secondary endpoints include progression-free survival, overall survival, pharmacokinetic parameters (Cmax and steady-state AUC), and anti-drug antibody formation rate, the last of which is standard for a biologic of this class. The broad tumor-agnostic enrollment in the escalation phase is consistent with an early-stage oncology drug development strategy that prioritizes dose characterization before indication-specific expansion.
The trial record excludes patients with active ocular disease and those with high bleeding risk factors. These exclusions are consistent with known class-level risks in TF-targeting ADCs — ocular toxicity and coagulopathy — observed with the approved predecessor in this target class, though the trial record does not explicitly state this rationale.
The science behind TF as an oncology target
TF, also designated CD142 or coagulation factor III, is overexpressed across a range of solid tumor types including cervical and pancreatic cancers, while expression in normal vasculature creates an on-target liability related to its role in the coagulation cascade. The target has been clinically validated by Genmab/Pfizer's tisotumab vedotin (Tivdak), which carries a monomethyl auristatin E (MMAE) microtubule-inhibiting payload and received US FDA approval for recurrent or metastatic cervical cancer.