Brenus Pharma has announced first data from the phase Ia dose escalation of BreAK CRC-001. Nine unresectable patients were treated; 89% had liver metastases and 89% KRAS-mutant tumours, a population refractory to immunotherapy.
95% of metastatic colorectal cancers are pMMR/MSS tumours, poorly immunogenic and resistant to immunotherapy. STC-1010, the company’s lead in vivo DC-engager, is designed to make these “cold” tumours visible to immune cells.
There was no dose-limiting toxicity, only grade 1–2 related adverse events. On clinical activity (seven evaluable patients), there was 100% disease control, with 57% objective response rate. Also, 43% of patients became operable (3/7); two showed no evidence of the disease afterward.
The ctDNA dropped by up to 97% within two months, and TP53 and KRAS mutations near undetectable.
The STC-1010 regimen nearly quadrupled cytotoxic CD8+ T-cell infiltration in tumours (+285% T2 vs baseline) and increased the CD4+/Treg ratio 2.5-fold. Circulating T cells increased, consistent with trafficking to the tumour. In the presented patient case, profiling showed intratumoral antigen-presenting macrophages, a peripheral shift of T cells toward a memory phenotype, and expansion of tumour-reactive PD-1+CD39+ cells.
“These data validate STC-1010’s safety. They reinforce our hypotheses with early efficacy signals and the potential to improve the therapeutic landscape of cold tumour,” said Paul Bravetti, CEO of Brenus Pharma.
“Making initially unresectable patients eligible for surgery is what matters most in first-line metastatic colorectal cancer. Seeing it alongside immune activation in MSS tumours is a remarkable signal for patients,” said François Ghiringhelli, Centre Georges-François Leclerc, Dijon, principal investigator.