A phase 1 study of CAN2109, a novel,long-acting, tumor-retained, immunogenic cell death inducer

The ongoing 3+3 Phase 1 study (NCT06332430/CTR20241484) enrolled solid tumours patients (pts) aged ≥18 years with at least one measurable lesion accessible for intra-lesional injection. The primary endpoint was the safety of CAN2109 administered Q3W defined as MTD and RP2D. Secondary endpoints were pharmacokinetics, pharmacodynamics and preliminary efficacy. Methods and Results As of December 16 2025, 19 pts (1-7 previous therapies, median 3 therapies) aged 28-66 years (median 48 years) with advanced/metastatic breast cancer (MBC) (7 HER2+, 6 HER2-), melanoma (1), sarcoma (2), thyroid (1), adenoid cystic (1) and sebaceous gland cancer (1) had been treated as 1 of 4 cohorts, 0.5mg (3 pts), 1.0 mg (3 pts), 2.0 mg (10 pts) and 4.0 mg (3 pts). The most common adverse events reported were local swelling, pain and inflammation at the injection site, mostly grade (Gr.) 1 or 2, controlled by transient dexamethasone employment locally. Two Gr. 3 event (ulceration with local infection in one pt) had been reported before dexamethasone introduction in MBC pts at 2.0 mg. Systemically, only Gr. 1 or 2 systemic adverse events have been observed, with 3 pts experiencing fever, 2 pts ALT increase, 2 pts anorexia, 1 pt vomiting and 1 pt fatigue. CAN2109 was mostly retained in the tumor after administered, with very low exposure in plasma. IP10 increased proportionally up to the dose of 2.0 mg. Higher CD3, CD8 and FOXP3 cells infiltration in tumour at baseline seemed to correlate with higher response rate. The MTD has been defined as 4.0 mg Q3W, and the RP2D as 2.0 mg Q3W. The RP2D cohort was expanded. Overall, 4 pts experienced a partial tumour response (PR) and 7 pts a disease stabilisation (SD), representing for a 22% overall response rate (ORR) and a 61% disease control rate (DCR). All the responders were treated in the 2mg dose cohort, and out of the total of 7 HER2+ MBC, 4 PR and 2 SD (ORR = 57%; DCR = 86%) were reported. Importantly, out of 5 MBC who had failed previous ADC treatments, 3 PR and 1 SD were shown. Abscopal effects were observed in 5 pts who received heavy pre-treatments, including the shrinkage or disappearance of metastases in bones, lungs and lymph nodes. Conclusion CAN2109 is a tumor-anchoring immunogenic cell death (ICD) inducer that can be administered to solid tumor pts with manageable toxicity. Preliminary efficacy data indicate activity in late stage HER2+ MBC, with some pts who failed previous ADC treatment. The RP2D cohort expansion is ongoing.