Phase Ib Basket Expansion Trial and Alternative-Schedule Dose-Escalation Study of ATR Inhibitor Elimusertib in Advanced Solid Tumors with DNA Damage Response Defects
Bibliographic record
Abstract
In this phase Ib basket expansion trial and alternative-schedule dose-escalation study, we evaluated the ataxia-telangiectasia and rad3-related (ATR) inhibitor elimusertib at 40 mg twice daily (3 days on/4 days off) in 143 patients with advanced cancer with tumor-associated DNA damage response defects, comprising gynecologic (n = 45), prostate (n = 19), colorectal (n = 24), and breast (n = 19) cancer, and ataxia-telangiectasia-mutated (ATM) loss (n = 36). An alternative schedule (3 days on/11 days off) was assessed in patients with ATM loss and/or ATM mutations (n = 32). Elimusertib-related reversible hematologic toxicities were observed. Objective responses were modest (4.5%), but a disease control rate (DCR) of 49.3% indicated that subpopulations of patients, especially those with gynecologic cancers (DCR 59.5%), derived meaningful, durable benefits from elimusertib. There was no association between ATM protein loss or ATM alterations and progression-free survival or overall response. Further studies to define optimal predictive biomarkers for ATR inhibitors, both as monotherapy and in combination, are ongoing. SIGNIFICANCE: This is the largest ATR inhibitor monotherapy study reported to date. A DCR of 49.3% indicated that subpopulations of patients, especially those with gynecologic cancers (DCR 59.5%), derived meaningful benefits from elimusertib. Biomarker studies suggest that early ctDNA response may potentially predict clinical benefit from ATR inhibitors.
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 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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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".