Systemic third generation allosteric STING agonist CRD3874-SI, a novel immunotherapy, in patients with advanced solid tumors: Results from a single-agent phase I study.

2661 Background: CRD3874-SI is a first in class, systemically administered, allosteric STING agonist that blocks STING’s proton channel activity differentiating it from previously developed STING agonists. The drug has demonstrated pre-clinical anti-cancer activity in several murine tumor models and has pharmacological properties distinct from earlier generation STING agonists. Methods: This is a single institution, open-label, phase I study of CRD3874-SI in patients with advanced solid tumors. The dose escalation study follows a standard 3+3 design. CRD3874-SI is administered intravenously once per week for 2 cycles. Cycle duration is 28 days. From cycle 3 onwards, continuous weekly treatment +/- one week break (week 4) may be considered. The primary objective is to assess the safety of CRD3874-SI by determining the maximum tolerated dose, recommended phase 2 dose and schedule of administration. Secondary objectives include examining the pharmacokinetics and pharmacodynamics (IP10 analysis) of CRD3874-SI and evaluating the efficacy of CRD3874-SI as determined by best objective response rate per RECIST v 1.1. Clinical trial information: NCT06021626. Research sponsor: Curadev Pharma, Inc. Results: As of January 5th 2026, 21 patients (sarcoma n=20, adenoid cystic carcinoma n=1) received treatment at four escalating dose levels (0.1-1.8mg/kg). The median number of prior lines of treatment was 4 (1-11). The median duration of treatment was 7 weeks (range: 1-32 weeks). 2 patients continue treatment. Reasons for treatment discontinuation include: progression of disease (n=16), toxicity (n=2), patient withdrawal (n=1). Treatment emergent adverse events (TEAEs) were manageable and reversible. Only low-grade cytokine related symptoms were reported. TEAEs possibly related to study treatment reported in >20% of participants and were mostly low grade include: fatigue (43%), chills (38%), nausea (38%), diarrhea (33% (G3 (10%)), headache (29%) and flu-like symptoms (24%). Low grade colitis not typical of auto-immune mechanism, responding well to temporary treatment pause +/- oral budesonide, were reported in 4 patients. One DLT at dose level 4 (G3 dyspnea) was observed. 19 patients are evaluable for efficacy. The best objective response per RECIST v1.1: confirmed partial response, n=1 (malignant phyllodes tumor); stable disease, n=9; progressive disease, n=9. Dose level 3 (0.9mg/kg) represents a biologically active dose (one confirmed PR and a second case with -27% tumor regression was observed). Dose proportional increase in AUC with concomitant increase in plasma CXCL10 levels were observed. Conclusions: CRD-3874-SI has demonstrated clinical activity with manageable safety. Dose level 0.9mg/kg is biologically and clinically active. A dose expansion phase at this dose level in is planned in >5 histology specific cohorts. Clinical trial information: NCT06021626 .