CStone Pharmaceuticals (2616) Study update summary

CS2009 design and study

• CS2009 is a trispecific antibody targeting PD-1, CTLA-4 and VEGF, designed to enhance tumor-microenvironment activity while limiting peripheral CTLA-4 toxicity; CTLA-4 is monovalent, with stated affinity of 20–30 nM.

• Phase I enrolled 72 heavily pretreated patients; 51% had prior immunotherapy, nearly 40% had received at least three prior therapies, and 54% were white.

• The global Phase I/II study is ongoing in Australia and China, with doses of 1–45 mg/kg every three weeks; Phase II dose expansion has begun and a US IND is in preparation.

Safety and pharmacology

• Grade ≥3 treatment-related adverse events were 30.9%, including 4.2% grade ≥3 immune-related events; management cautioned that rates could rise as follow-up matures.

• No grade 4/5 treatment-related adverse events or dose-limiting toxicities were reported; common events included fatigue, nausea, headache and rash.

• VEGF-related events included two hypertension cases, one proteinuria case and one hemorrhage attributed to a patient with a duodenal ulcer.

• PK was dose-proportional, with a 6–8-day half-life and minimal accumulation; peripheral receptor occupancy saturated at doses ≥20 mg/kg, while pharmacodynamic markers plateaued around 10 mg/kg.

• Free serum VEGF-A fell below 10 pg/mL after 1 mg/kg and remained suppressed across reported dose levels; T-cell activation markers increased dose-dependently.

Early antitumor activity

• Overall ORR was 14.3% and DCR 71.4% at a median follow-up of ~2 months; response data remained immature.

• In post-IO NSCLC, ORR was 17.6%; among 12 patients excluding EGFR-mutant cases, ORR was 25% and DCR 83.3%.

• Activity was reported across NSCLC, ovarian cancer, TNBC, non-clear-cell RCC and soft-tissue sarcoma; a sarcoma patient remained on treatment with tumor reduction above 40%.

• Disease-control durations extended to seven or eight months in lower-dose patients, while many higher-dose patients remained on treatment; higher-dose cohorts showed a dose-dependent efficacy trend.