BOLD-100-001 (TRIO039): A phase 1b dose-escalation study of BOLD-100 in combination with FOLFOX chemotherapy in patients with advanced gastrointestinal solid cancers: Interim safety, tolerability, and efficacy.
Bibliographic record
Abstract
3031 Background: BOLD-100 is a first-in-class ruthenium-based anticancer agent in Phase 1b / 2 clinical development for the treatment of advanced gastrointestinal (GI) cancers in combination with FOLFOX. Being developed primarily as a combinational agent, BOLD-100 induces cellular stress through modulation of the unfolded protein response, production of reactive oxygen species and induction of DNA damage. BOLD-100 demonstrates synergy in established preclinical models in combination with various anticancer therapies, particularly in resistant cell lines. Methods: This is a prospective, Phase 1b dose-escalation (Part A) and Phase 2 dose-expansion (Part B) study of BOLD-100 in combination with FOLFOX for colorectal (CRC), pancreatic (PDAC), gastric (GC) and biliary tract (BTC) cancers. Patients (pts) receive BOLD-100 with FOLFOX on day 1 of each 14-day cycle. In Part A, pts are enrolled in a 3+3 design to determine the combination recommended Phase 2 dose (RP2D), with BOLD-100 dose-escalation (420, 500 and 625 mg/m2) up to dose level 3. Part B comprises 5 cohorts treated at the RP2D until progressive disease or unacceptable toxicity. In Part A, reported here, the primary endpoints are safety, tolerability and maximum tolerated dose; the Part B endpoints are efficacy (primary), pharmacokinetic (PK) and pharmacodynamic parameters (secondary), and duration of response (exploratory) (NCT04421820). Results: As of 07 Feb 2022 (contains Part A preliminary data), 19 pts (mean age 65 years) were treated: 9 (47%) CRC, 5 (26%) BTC, 4 (21%) PDAC, 1 (5%) GC. Patients had a median of 3 prior systemic therapies, and 18 (95%) were enrolled with stage IV disease. Median number of cycles completed was 5 (range 1-15). 18 pts reported ≥1 treatment-emergent adverse events (AEs), most commonly fatigue (n = 12, 63%), nausea (n = 9, 47%) and stomatitis (n = 8, 42%). The majority of AEs were grade (G) 1-2. 7 G4 AEs (all neutropenia), and 1 unrelated G5 AE of pulmonary embolism occurred. There were 8 serious AEs in 6 different pts, with 1 SAE of dyspnea reported as related to BOLD-100. 2 pts experienced infusion-related reactions, related to chemotherapy. 2 dose-limiting toxicities have been observed: G3-4 neutropenia complicated by fever > 38.5°C or infection (n = 1, cohort #2) and inability to receive planned doses due to AEs (n = 1, cohort #3). To date for evaluable pts (n = 16), disease control rate of 75%, 1 partial response (48% target lesion reduction) and 11 stable disease have been observed. Conclusions: BOLD-100 plus FOLFOX is well-tolerated with no clinically significant safety findings. Dose-escalation data supports a BOLD-100 RP2D of 625 mg/m2 for the expansion phase. Progression-free survival, overall survival, and PK data are forthcoming. Clinical trial information: NCT04421820.
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How this classification was reachedexpand
Direct model labels (unvalidated)
Per-model category and study-design labels from the labeling rounds. They are machine output, unvalidated, and the disagreement between models ships as data. No study design here is MEDLINE-validated yet.
| Model arm | Categories | Study design | Confidence |
|---|---|---|---|
| gemma | no category Domain: not available · Genre: Empirical About the Canadian research system: no · About a Canadian topic: no | Non-randomized trial | low |
| gpt | no category Domain: not available · Genre: Empirical About the Canadian research system: no · About a Canadian topic: no | Non-randomized trial | medium |
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 | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.004 |
| Insufficient payload (model declined to judge) | 0.004 | 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, unvalidatedLabeled directly by 2 models reading the full record.
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".