58O - Clinical efficacy, safety, and PK/PD from the first in human study of BM201, a TLR7/8 agonist

Background

For the design of a vaccine, antigen and adjuvant are necessary for effective immune response. In the context of therapeutic tumor vaccination, in situ vaccination has attracted more and more attention as it makes tumor to provide antigens through radiotherapy or intratumoral (i.t.) delivery of immunotherapeutics. BM201 was developed as a selective TLR7/8 agonist uniquely designed for i.t. administration, aiming to effectively activate antigen-presenting cells and enhance the immunogenicity of tumor antigens through the synergistic combination with radiotherapy by more effectively presenting the tumor antigens exposed by radiotherapy to T cells.

Methods

This is an open-label, first-in-human phase I multiple ascending-dose study investigating BM201 in combination with hypofractionated radiotherapy (5-8Gy, 4 fractions) in patients with refractory or metastatic solid tumors. The dose escalation part assessed doses from 24 mg up to 240 mg administered i.t. every 2 weeks. Primary objective was safety and tolerability. Secondary endpoints included PK and preliminary anti-tumor activity according to RECIST 1.1.

Results

Till May 30, 2024, 17 patients had been treated with BM201. Notably, 64.7% of the patients had soft tissue sarcomas, and 64.7% of them had been unresponsive to immunotherapy, having received prior PD-1 treatment. Plasma exposure increased with dose. A sustained-release PK characteristic was observed in most patients experiencing tumor shrinkage. Abscopal effects were observed in 29.4% of the patients. The objective response rate (ORR) was 5.9 %, and disease control rate (DCR) was 58.8 %. For the injected lesions, the ORR was 11.8 % and DCR was 88.2 %. At higher doses, the ORR rate was 10%, with a DCR of 60%. Specifically for injected lesions, the ORR rate was 20%, achieving a DCR of 80%. The majority of TRAEs were grade 1-2. Grade 3 TRAEs included lymphocytopenia, anemia, diarrhea and prolonged QT interval on ECG. No grade 4-5 TRAEs or dose limiting toxicity was observed.

Conclusions

BM201 has a favorable safety profile and has shown encouraging anti-tumor activity in the dose escalation phase. Follow-up is still ongoing.

Clinical trial identification

NCT06368960.

Editorial acknowledgement

Legal entity responsible for the study

InnoBM Pharmaceutics Co. Ltd.

Funding

InnoBM Pharmaceutics Co. Ltd.

Disclosure

All authors have declared no conflicts of interest.