NEW YORK – Boundless Bio said on Thursday that it has started treating patients in a Phase I/II trial of its ribonucleotide reductase (RNR) inhibitor BBI-825 for the treatment of locally advanced or metastatic cancer with resistance gene amplifications.
The Phase I portion of the STARMAP trial will include 42 participants to evaluate BBI-825 as a monotherapy and in combination with other targeted therapies. The company developed BBI-825 as a potential treatment for oncogene amplifications associated with resistance to targeted therapy treatment of MAPK pathway-activated cancers, Klaus Wagner, chief medical officer at Boundless Bio, said in a statement.
The first part of the trial will evaluate different doses of BBI-825 monotherapy. The second part will explore different doses of BBI-825 with either Pfizer's BRAF inhibitor Braftovi (encorafenib) and Eli Lilly's EGFR inhibitor Erbitux (cetuximab) or with Bristol Myers Squibb's KRAS inhibitor Krazati (adagrasib) and Erbitux in patients with advanced or metastatic colorectal cancer harboring BRAF V600E or KRAS G12C mutations and co-occurring resistance gene amplifications. Part three of the trial will be a dose expansion study of BBI-825 plus the targeted therapy combinations at the doses identified in the earlier stages of the study.
"If data are supportive, we may have the opportunity to expand into broader patient populations, including pan-tumor, pan-RAS, and pan-RAF indications, potentially addressing these populations of cancer patients with very high unmet need," Boundless CEO Zachary Hornby said in a statement.
BBI-825 is Boundless' second extrachromosomal DNA (ecDNA) candidate to enter clinical trials. The San Diego-based firm has found that targeting ecDNA can address a root cause of oncogene amplification. Last year, Boundless began a Phase I/II trial for its first ecDNA clinical program, CHK1 inhibitor BBI-355, in advanced or metastatic solid tumors with oncogene amplifications.