CS2009 PD-1/VEGF/CTLA-4 trispecific posts 18.5% ORR in heavily pretreated NSCLC (no actionable drivers)

CS2009 is a first-in-class trispecific antibody designed to simultaneously block PD-1 and CTLA-4 immune checkpoints while neutralizing VEGF (anti-angiogenesis), evaluated in an open-label, multicenter Phase 1 dose-escalation/backfill first-in-human study (NCT06741644) in advanced solid tumors after progression on—or lack of—standard therapy (n=98; data cutoff January 4, 2026). No DLTs were observed and MTD was not reached; any-grade/grade≥3 TRAEs were 69.4%/20.4%, with pruritus (14.3%), ALT increase (11.2%), and AST increase (10.2%) most common; 5.1% discontinued for TRAEs and there were no treatment-related deaths. Preliminary activity in heavily pretreated subsets included ORR/DCR of 18.5%/74.1% in NSCLC without known actionable alterations (n=27), 33.3%/66.7% in soft tissue sarcoma (n=9), 20.0%/100% in non-clear cell RCC (n=5), and 16.7%/50.0% in TNBC (n=6)—roughly in the same ballpark as single-agent PD-1 activity in unselected sarcoma (~18% ORR in SARC028) and notably below what’s typically seen with active targeted/IO combinations in nccRCC (e.g., nivo+cabo ORR reported in a Phase 2 nccRCC study), with TNBC benchmarking complicated by the now-established role of TROP2 ADCs like sacituzumab govitecan in later lines.