Clinical efficacy and safety of BM201 intra-tumoral injection and radiotherapy in advanced solid tumors: Results from the phase I/IIT study.

2599 Background: For vaccine design, an antigen and an adjuvant are necessary for an effective immune response. In the context of therapeutic tumor vaccination, in situ vaccination has garnered increasing attention as it enables tumors to provide antigens through radiotherapy or intra-tumoral (i.t.) delivery of immunomodulators. BM201, a selective TLR7/8 agonist uniquely designed for intra-tumoral (i.t.) administration, aims to effectively activate antigen-presenting cells and enhance immunogenicity through combination with radiotherapy by more effectively presenting the tumor antigens exposed to T cells. When combined with intravenous (i.v.) infusion of αPD-1 monoclonal antibody (mAb), it relieves tumor immunosuppression and exerts synergistic anti-tumor effects. Methods: This is an open-label, exploratory, and phase I/IIT study. Phase I portion was a dose-escalation study designed to investigate BM201 (dose range: 24-240mg, i.t. every 2 weeks) in combination with hypofractionated radiotherapy (5-8Gy, 4 fractions) (R-ISV-BM201) in patients with refractory or metastatic solid tumors. Phase IIT portion was designed to investigate BM201 (dose range: 24-240mg, i.t. every 3 weeks) in combination with hypofractionated radiotherapy (5-8Gy, 4 fractions) plus αPD-1 (200mg, i.v. every 3 weeks) (R-ISV-BM201 + αPD-1) in patients with refractory or metastatic soft tissue sarcomas. Primary objective of both 2 studies was safety and tolerability. Secondary endpoints included PK and preliminary anti-tumor activity according to RECIST 1.1 in Phase I, while anti-tumor activity according to irRECIST 1.1 in Phase IIT. Results: Till December 05, 2025, 29 patients had been treated with BM201 (19/29 in Phase I, 10/29 in Phase IIT). Among the 29 patients, 51.7% had been unresponsive to immunotherapy (prior αPD-1). Plasma exposure increased with dose. A sustained-release PK characteristic was observed in most patients experiencing tumor shrinkage. Abscopal effects were observed in 31.6% (6/19) and 50% (5/10) of patients in Phase I and Phase IIT, respectively. In Phase I, the objective response rate (ORR) was 5.2%, and the disease control rate (DCR) was 84.2%; while these were 10.5% and 84.2% in injected lesions. In Phase IIT, the ORR was 20%, and the DCR was 100.0%; while these were 46.1% and 92.3% in injected lesions. The median progression-free survival was 7.7 months, the median overall survival was 17.0 months, and the median duration of response in injected lesions was 5.6 months. The majority of TRAEs were grade 1-2. Grade 3-4 TRAEs mainly included lymphocytopenia, anemia, thrombocytopenia, and hypertension. No grade 5 TRAEs or dose-limiting toxicity was observed. Conclusions: R-ISV-BM201 has a manageable safety profile and has shown encouraging anti-tumor activity. A trigger systemic immune response would be expected when it is synergized with αPD-1 mAb. Clinical trial information: Phase I: NCT06368960 ; Phase IIT: ChiCTR2300077953.