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).
Bibliographic record
Abstract
4115 Background: BOLD-100 is a first-in-class ruthenium-based anticancer agent in Phase 2 clinical development for the treatment of advanced gastrointestinal (GI) cancers in combination with FOLFOX. BOLD-100 demonstrated synergy in established preclinical models in combination with various anticancer therapies. Methods: In this prospective Phase 2 study, patients with pretreated advanced biliary tract cancers (BTC) received BOLD-100 (625 mg/m2) in combination with FOLFOX on day 1 of each 14-day cycle until progressive disease or unacceptable toxicity. The primary objective was to evaluate the efficacy of BOLD-100 in three clinical endpoints (PFS, OS, and ORR). Disease Control Rate (DCR) was also determined. Bayesian modelling was used to continually reassess these endpoints, the posterior probability of superiority to an historical landmark for each endpoint. Results: As of 31 Dec 2023, 22 pts with advanced metastatic BTC (5 gall bladder, 5 intrahepatic, 8 distal, 1 perihilar, and 3 unk) were enrolled and treated in the study. At enrollment, pts had a median age of 61 years [range 33, 81] and had a median of 10.9 months from diagnosis of metastatic disease. All patients were ECOG ≤ 1. Patients had a median of 2 prior systemic therapies [range 1, 5] with 13 receiving 2 or more prior regimens. 21/22 BTC patients received prior GEM/CIS, 8 pts had prior 5-FU treatment and 6 prior IO. On study, pts received a median of 4 cycles BOLD-100 + FOLFOX [range 1, 41]. Median PFS was 6.0 [95% credible interval (CI) 3.8, 10] months, median OS 7.3 [CI 4.5, 13] months, ORR 6% [1,23] and DCR 83% [62, 95] in the 18 evaluable patients. Six patients had reductions in their target lesions with 1 partial response. Study treatment was well tolerated. For the 22 treated patients, 21 reported 1 or more treatment-related adverse events (AEs), most commonly neutrophil count decreased (n=10, 46%), nausea (n=8, 36%), fatigue (n=7, 32%), peripheral sensory neuropathy (n=6, 27%), and pyrexia (n=6, 27%). Nine patients (41%) reported G3/4 neutrophil count decreased. Conclusions: BOLD-100 combined with FOLFOX is an active and well-tolerated treatment regimen in Stage IV BTC. There were no new safety signals detected. The mPFS, mOS, ORR and DCR data in this advanced BTC cancer population indicate a treatment combination worthy of further study for this difficult to treat cancer. Clinical trial information: NCT04421820 .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".