BOLD-100-001 (TRIO039): A phase Ib dose-escalation study of BOLD-100 in combination with FOLFOX chemotherapy in patients with advanced gastrointestinal solid tumors.
Bibliographic record
Abstract
TPS145 Background: Although most cancers are initially susceptible to existing anticancer therapies, over time cancer cells develop resistance. BOLD-100 is a first-in-class therapy that targets the GRP78 pathway, a major regulator of cellular stress and resistance. This therapy suppresses drug resistance, survival and proliferation by restraining stress-induced upregulation of GRP78 in tumor cells, leading to inhibition of the cell survival response. BOLD-100 successfully completed a Phase 1 monotherapy trial, with a manageable safety profile; it has demonstrated synergy in established preclinical models in combination with a wide variety of anticancer therapies and shown to restore sensitivity of drug-resistant cell lines. Methods: BOLD-100-001 is a multicenter, prospective, two-stage, non-randomized Phase 1b dose escalation and expansion study of BOLD-100 in combination with FOLFOX chemotherapy for selected advanced solid gastrointestinal (GI) tumors: colorectal (CRC), pancreatic (PANC), gastric (GC) and bile duct cancers (BDC). Each patient will receive BOLD-100 along with FOLFOX chemotherapy on Day 1 of each 14-day cycle. In the dose-escalation phase (Part A), patients will be enrolled to determine the combination recommended dose using a standard 3+3 design. In the dose-expansion phase (Part B), up to 80 patients with selected GI tumors will be enrolled in 5 cohorts (comprising the 4 GI cancers referred) and treated with BOLD-100 at the recommended dose and FOLFOX, until progressive disease or unacceptable toxicity. In Part A dose-escalation, the primary objective is to assess the safety, tolerability and maximum tolerated dose. The Part B dose-expansion will assess the efficacy (progression free survival, overall survival and response rate), of FOLFOX chemotherapy plus BOLD-100. Secondary objectives in Part A and B include the assessment of pharmacokinetic and pharmacodynamic parameters and potential biomarkers predictive of efficacy. Eligible patients will have previously treated histologically/cytologically confirmed metastatic/unresectable GI tumor (CRC, PANC, GC or BDC), measurable disease per RECIST criteria, an ECOG performance score of 0 or 1, and adequate organ function. In Part A, no formal statistical hypotheses will be tested; analysis of the data will focus on comparisons of safety and dose-limiting toxicities between cohorts and only descriptive methods will be used. In Part B, Bayesian modelling will be used to continually reassess the efficacy endpoints: progression free survival, overall survival and objective response rates. The study was opened for enrollment in August 2020; approximately 25-30 patients will be screened to achieve up to 20 patients in Part A and up to 80 patients will be enrolled in Part B with a maximum of 25 patients per arm. Clinical trial information: NCT04421820.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".