A phase 1/2 open-label study of safety and antitumor activity of EPI-506, a novel AR N-terminal domain inhibitor, in men with metastatic castration-resistant prostate cancer (mCRPC) with progression after enzalutamide or abiraterone.
Bibliographic record
Abstract
TPS5072 Background: EPI-506 is a first-in-class, highly specific small molecule inhibitor of the androgen receptor (AR) N-terminal domain (NTD). In vitro and in vivo studies have shown activity against full length AR and constitutively active AR splice variants, including AR-V7 (associated with resistance to abiraterone and enzalutamide). EPI-506 is expected to be effective in mCRPC driven by both canonical and aberrant AR signaling by targeting the NTD common to full length and splice variant AR. Initial clinical development of EPI-506 will target mCRPC with progression after prior enzalutamide and abiraterone. Methods: This open-label, single-arm, phase 1/2 study will evaluate the benefit of 12 week once-daily dosing with EPI-506, after establishing the safety, pharmacokinetics (PK), and optimal dose of EPI-506 in single- and multiple-dose escalations. The study will involve ~20 investigational sites in the US and Canada, and is expected to launch in Q2 2015. The planned enrollment is 150 patients. Inclusion criteria include mCRPC with progression after one or more lines of hormonal therapy or chemotherapy, and progression on enzalutamide or abiraterone. Exclusion criteria include hematologic, hepatic or renal insufficiency. The phase 2 portion of the study will evaluate activity in 3 patient populations: post-enzalutamide mCRPC, post-abiraterone mCRPC, and enzalutamide/abiraterone naïve mCRPC. Primary endpoints include PSA response at week 12, defined as a ≥ 50% PSA decrease from baseline. Secondary endpoints include: PK, objective RECIST response, time to PSA progression, radiographic progression-free survival, and safety/tolerability. Exploratory endpoints include evaluation of AR splice variants and AR mutations from CTC-based and ctDNA-based methodologies, as well as molecular characterization of optional tissue biopsies. This trial will be the first to evaluate the novel NTD inhibitor EPI-506 in men with enzalutamide- and/or abiraterone-failure mCRPC, and is the first agent with the potential to inhibit both canonical and variant-mediated AR signaling.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 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".