CS2009, a novel PD-1/VEGF/CTLA-4 trispecific antibody, in patients with advanced solid tumors: Updated results from an open-label, multicenter, phase 1 first-in-human study.

Abstract

2521 Background: CS2009 is a first-in-class trispecific antibody targeting PD-1, VEGF and CTLA-4. Initial data from this phase 1 study showed a favorable safety profile and encouraging antitumor activity. Here, we report updated safety and efficacy results in 98 patients. Methods: This ongoing, open-label, multicenter, phase 1 dose-escalation trial enrolled patients with advanced solid tumors who progressed on standard therapy or had no available standard therapy. CS2009 was administered intravenously every 3 weeks at 6 dose levels ranging from 1 to 45 mg/kg. Dose escalation followed an accelerated titration design at the first dose level and a 3+3 design thereafter. In parallel, additional patients were backfilled to selected dose levels deemed safe to further evaluate safety and efficacy. Primary objectives include safety, tolerability and determination of the maximum tolerated dose (MTD)/tentative recommended phase 2 dose (RP2D). Secondary and exploratory objectives include pharmacokinetic/pharmacodynamic profile and preliminary efficacy per RECIST v1.1, etc. Results: As of January 4, 2026, 98 patients (55.1% male; median age 61 [range 19-80] years; 54.1% Asian, 43.9% White) had received CS2009 across 6 dose levels, with half (49/98) remaining on study treatment. Tumor types included non-small cell lung cancer (NSCLC, n = 49), ovarian cancer (n = 12), soft tissue sarcoma (n = 9), renal cell carcinoma (RCC, n = 6), triple-negative breast cancer (TNBC, n = 6), colorectal cancer (n = 4), and others. Most (98.0%) patients received at least one prior line of systemic anti-cancer therapy. No dose-limiting toxicities (DLTs) occurred; MTD was not reached. The incidences of any-grade and grade ≥3 treatment-related adverse events (TRAEs) were 69.4% and 20.4%, respectively. The most common (≥10%) TRAEs were pruritus (n = 14, 14.3%), alanine aminotransferase increased (n = 11, 11.2%) and aspartate aminotransferase increased (n = 10, 10.2%). Five (5.1%) patients discontinued treatment due to TRAEs. There were no treatment-related deaths. Encouraging antitumor activity was observed across multiple tumor types that have received heavy prior treatment including PD-1/PD-L1 inhibitors or antiangiogenesis therapies where appropriate, including NSCLC without known actionable oncogenic alterations (n = 27), soft tissue sarcoma (n = 9), non-clear cell RCC (n = 5), and TNBC (n = 6) with ORR of 18.5%, 33.3%, 20.0%, 16.7%, respectively, and DCR of 74.1%, 66.7%, 100.0%, 50.0%, respectively (detailed and updated data to be presented at the conference). Conclusions: CS2009 demonstrated a manageable safety profile and promising antitumor activity in heavily pretreated patients with advanced solid tumors, which warrants further clinical development in an ongoing phase 2 study in nine tumor types. Clinical trial information: NCT06741644 .