CStone Pharmaceuticals presented multiple key clinical updates for its core asset CS2009 (a PD-1/VEGF/CTLA-4 trispecific antibody) in two posters at the American Society of Clinical Oncology Annual Meeting, covering Phase I/II clinical data in first-line and later-line NSCLC and CRC patients, as well as mature Phase I data from longer follow-up in patients with advanced solid tumors. In first-line non-small cell lung cancer (NSCLC) patients with high PD-L1 expression (TPS =50%), CS2009 monotherapy achieved an objective response rate (ORR) of 81.3% and a disease control rate (DCR) of 100.0%, with consistent benefit across squamous (ORR: 87.5%) and non-squamous (ORR: 75.0%) histologies. In the PD-L1-negative/low population (TPS =5%) squamous NSCLC cohort, CS2009 in combination with chemotherapy achieved an ORR of 75.0% and a DCR of 100.0%; notably, PD-L1-negative patients within this cohort achieved an ORR of 100.0%.
The current efficacy readout remains immature due to the short follow-up for most patients in this cohort. In heavily pretreated later-line NSCLC, CS2009 demonstrated encouraging antitumor activity, with most patients experiencing sustained tumor shrinkage. Across all dose levels, the 6-month duration of response (DOR) rate reached 85.7%.
In the second-/third-line combination cohort, CS2009 achieved an ORR of 66.7% and a DCR of 100.0%. In the 30 mg/kg monotherapy cohort, patients whose disease had progressed following prior immunotherapy plus platinum-based chemotherapy achieved an ORR of 30.8% and a DCR of 84.6%. In 'cold tumors' with limited immunotherapy responsiveness, CS2009 monotherapy produced a 25.0% ORR and 87.5% DCR in heavily pretreated proficient mismatch repair/microsatellite stable metastatic colorectal cancer (pMMR/MSS mCRC).
A 66.7% ORR and 100.0% DCR were observed when CS2009 was combined with XELOX in first-line mCRC. The current efficacy readout remains immature due to the short follow-up for most patients in these two CRC cohorts. Additional monotherapy activity was seen in soft tissue sarcoma (STS) and non-clear cell renal cell carcinoma (nccRCC) (ORR 33.3% each).
With extended follow-up since initial presentation at European Society for Medical Oncology Congress 2025, updated Phase I safety data further confirmed the well-tolerated profile of CS2009. No excessive toxicities typically associated with CTLA-4/PD-(L)1 combinations observed. Among heavily pretreated patients with advanced solid tumors, Grade =3 treatment-related adverse events (TRAE) occurred in 24.6% of patients, immune-related adverse events (irAE) in 12.7%, and TRAE possibly related to anti-VEGF in 5.1%.
This favorable safety profile was consistently maintained across both monotherapy and chemotherapy combination cohorts in first-line NSCLC. The ongoing global Phase I/II trial has enrolled nearly 300 patients across China and Australia, with U.S. Investigational New Drug clearance now obtained. CStone plans to initiate the first Phase III global multi-regional registrational trial (MRCT) for CS2009 by the end of 2026.
