KEY TAKEAWAYS
- The phase 1 & 2 trial aimed to assess the efficacy of treatment with BOLD-100 + FOLFOX post-standard FOLFOX/CAPOX treatment in pts with mCRC.
- The primary objective were to determine PFS, OS, and ORR.
- BOLD-100 + FOLFOX shows promise in treating heavily pretreated mCRC; further investigation is ongoing.
BOLD-100 being a ruthenium-based compound that potentially targets GRP78, regulates the unfolded protein response. It induces reactive oxygen species generation causing DNA damage and ceasing the cell cycle. This mechanism leads to cell death in a range of cancers, including varieties resistant to existing treatments.
Grainne M. O’Kane and the team designed this study to investigate the safety and efficacy of BOLD-100 with FOLFOX (BOLD-100 + FOLFOX) in patients (pts) with metastatic colorectal cancer (mCRC) who already underwent standard treatments, including FOLFOX or CAPOX (FOLFOX/CAPOX).
Enrolled pts were administered with a dose of 625 mg/m2 of BOLD-100 + FOLFOX (on day 1 per 14-day cycle), with consistent treatment until disease progression or unacceptable toxicity. The primary goal of the study was to evaluate progression-free survival (PFS), overall survival (OS), and objective response rate (ORR), with an elaborative determination of the disease control rate (DCR) in already treated pts.
As of March 14, 2024, total 38 pts with advanced relapsed/refractory mCRC, post-2 lines of therapy, participated in the study. The median age of the pts was 62 years (range 40-78), with 53% being women.
All pts had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 (26%) or 1 (74%). On average pts were subjected to 4 prior systemic therapies (range 2-8), a median of, and nearly all but one patient had stage IV disease. Pts received a median of 6 cycles of BOLD-100 + FOLFOX (range 1-18).
Outcomes of the study revealed a median PFS of 4.2 months (95% credible interval 3.0, 6.0), and a median OS of 8.3 months (5.7, 13). The ORR was 10% (3, 24), with a DCR of 77% (61, 89) among the 31 evaluable pts.
Notably, 3 pts achieved a partial response, and 2 pts experienced tumor lesion decreases between 20-29%. Treatment with BOLD-100 plus FOLFOX was generally well tolerated, with the most common treatment-related adverse events (AEs) including neutropenia (47%), nausea (42%), vomiting (21%), fatigue (21%), infusion-related reactions (21%), and pruritus (16%).
Most of these AEs were of grade 1-2, although 42% of pts encountered grade 3/4 neutropenia. Peripheral neuropathy, typically associated with oxaliplatin treatment, was reported in less than even 5% pts of grades 1-2.
The study concluded that BOLD-100 + FOLFOX shows promise as an effective and well-tolerated treatment for heavily pretreated pts with mCRC, offering clinical benefits with minimal neuropathy and significant toxicities. Further investigation of this treatment combination is warranted to address the unmet needs in mCRC therapy.
The trial was sponsored by Bold Therapeutics Inc.
Source: https://cslide.ctimeetingtech.com/esmogi24hybrid/attendee/confcal/show/session/3
Clinical Trial: https://www.clinicaltrials.gov/study/NCT04421820
O’Kane G M, Spratlin J, Oh D Y, et al. (2024). “BOLD-100-001: A phase II study of BOLD-100 in combination with FOLFOX in advanced mCRC patients that have failed at least two prior lines of therapy.” Presented at ESMO-GI 2024, (Abstract 44P).
