BOLD-100, a novel ruthenium-based anticancer drug, is currently undergoing phase 2 clinical trials for the treatment of advanced gastrointestinal cancers when used alongside FOLFOX. Preclinical studies have shown that BOLD-100 works synergistically with different anticancer treatments and has the potential to be efficacious in a broad range of tumor types. The interim efficacy and safety data in patients with pretreated, advanced metastatic biliary tract cancer (BTC) who have progressed on standard-of-care gemcitabine-cisplatin (gem/cis)-based regimens were presented at ASCO 2024.
In this phase 2 clinical trial, individuals with previously treated advanced BTC were administered BOLD-100 (625 mg/m2) along with FOLFOX on the first day of every 14-day cycle until disease progression or intolerable side effects. The primary objective was to assess progression-free survival (PFS), and secondary objectives included overall survival (OS), overall response rate (ORR), duration of response (DOR), and safety and tolerability. Additionally, disease control rate (DCR) was calculated. The safety analysis included all patients who received ≥1 doses of any study drug, and the efficacy analysis included all patients who had a baseline and ≥1 post-baseline assessments or discontinued study treatments due to progressive disease or death. Bayesian modeling was employed to consistently re-evaluate these outcomes and the likelihood of BOLD-100’s superiority compared with a historical benchmark for each outcome.
As of December 13, 2023, a total of 22 patients with advanced metastatic BTC were enrolled and treated in the study. The median age was 61 years at enrollment, and patients had a median of 10.9 months from the diagnosis of metastatic disease. All patients had an ECOG performance status score ≤1. Patients had a median of 2 prior systemic therapies. All 22 patients received prior gem/cis, with 8 having prior 5-fluorouracil treatment and 6 prior immunotherapies. During the study, the patients received a median of 4 cycles of BOLD-100 + FOLFOX (range, 1-41). Efficacy results from the evaluable population (n=18) demonstrated a median PFS was 6.0 months (95% confidence interval [CI], 3.8-10). The median OS was 7.3 months (95% CI, 4.5-13), the ORR was 6% (95% CI, 1-23), and the DCR was 83% (95% CI, 62-95), in the 18 evaluable patients. Six patients saw reductions in their target lesions, resulting in 1 partial response. All patients in the safety analysis (n=21) reported experiencing ≥1 any-grade treatment-related adverse events, with the most common being a decrease in neutrophil count (n=10; 46%), nausea (n=8; 36%), fatigue (n=7; 32%), peripheral sensory neuropathy (n=6; 27%), and pyrexia (n=6; 27%). Additionally, 16 patients experienced a grade ≥3 adverse event with the most common being neutrophil count decrease (41%), anemia (18%), and neutropenia (18%).
The combination of BOLD-100 and FOLFOX has proven to be an effective and well-tolerated treatment regimen for pretreated, advanced metastatic BTC. No additional safety concerns were identified. The median PFS, median OS, ORR, and DCR data in this group of advanced BTC patients suggest that this treatment combination merits further investigation for this challenging cancer type.
O’Kane GM, Oh DY, Spratlin J, et al. A phase 2 study of BOLD-100 in combination with FOLFOX chemotherapy in patients with pretreated advanced biliary tract cancer: efficacy and safety analysis (BOLD-100-001). Chicago, IL, & online: presented at 2024 ASCO Annual Meeting; abstract 4115.
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