Phase Ib study of niraparib plus androgen receptor-targeted therapy (ART) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).
Bibliographic record
Abstract
122 Background: Poly ADP-ribose polymerase (PARP) inhibitor and abiraterone acetate + prednisone (AA+P) has activity in pts with mCRPC regardless of DNA repair gene defects (DRD). Methods: This phase 1b study (Bedivere; NCT02924766) began with a 3+3 dose escalation of niraparib (Part 1), followed by expansion (Part 2) of the recommended phase 2 dose (RP2D) of nira + AA+P. Pts with mCRPC received nira 200 or 300 mg/day with AA+P. Dose-limiting toxicities (DLTs) were evaluated the first 28 days. Serial PK for nira were collected on cycle 1 day 1 (C1D1) over 24 h; PK for nira and abiraterone were collected on C2D1 over 10 h. Results: Nira 200 mg + 1000 mg AA+P was selected as the RP2D dose. 4 pts in 200 mg cohort and 8 pts in 300 mg cohort were enrolled in Part 1. During Part 1, 1 patient in the 300 mg cohort had two DLTs: Gr 3 fatigue and Gr 4 increased gamma glutamyltransferase. Therefore, the 200 mg dose was evaluated in 15 pts in Part 2. In 19 total pts treated with 200 mg niraparib, 12 (63%) pts had Gr 3-4 AEs, 5 (26%) pts had an AE with outcome of drug discontinuation and 1 (5%) patient had an AE with outcome of death (general physical health deterioration; unrelated). AEs of special interest were: 6 pts (32%) thrombocytopenia, 6 pts (32%) hypertension, 5 pts (26%) anemia and 3 pts (16%) neutropenia of any grade. 21% pts in 200 mg cohort had treatment emergent serious AE (TESAE) while 50% treated with 300 mg had TESAE. The exposure (AUC24h) on Day 1 of Cycle 2 for 200 mg niraparib with 1000 mg of AA were 17745±9380 ng.h/mL and 712±140 ng.h/mL, respectively. These exposures are consistent with single agent PK. Summaries of all responses will be provided, including a patient with primarily bone disease and carrying an ATM mutation who had a circulating tumor cell conversion and was on study treatment for 22.1 mo. Conclusions: The safety and PK findings support the choice of nira 200 mg in combination with AA+P in pts with mCRPC. The efficacy of nira + AA+P is being evaluated in an ongoing phase 3 MAGNITUDE study (NCT03748641). Clinical trial information: NCT02924766.
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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) | 0.002 | 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) | 0.005 | 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".