Phase II study of niraparib in patients with metastatic castration-resistant prostate cancer (mCRPC) and biallelic DNA-repair gene defects (DRD): Preliminary results of GALAHAD.
Bibliographic record
Abstract
202 Background: New therapies are needed for patients (pts) with mCRPC progressing after androgen-receptor signaling inhibitors (ARSIs) and taxane therapies. Niraparib is a once daily highly selective inhibitor of poly (ADP-ribose) polymerase (PARP-1 and 2). Methods: GALAHAD is an ongoing open label Ph 2 study assessing niraparib (300 mg daily) in pts with DRD progressing on/after ARSIs and taxane chemotherapy. Using a validated plasma assay, DRD status was defined as pathogenic mutations (including homozygous deletions) of BRCA1/2, ATM, FANCA, PALB2, CHEK2, BRIP1 or HDAC2. Composite response rate (RR) was defined as an objective response by RECIST 1.1 for measurable disease, circulating tumor cell (CTC) conversion to < 5/7.5 mL blood or prostate-specific antigen (PSA) decline of ≥50% (PSA50). Here, preliminary data on RR and adverse events (AEs) are reported in pts with biallelic DRD. Results: As of 10 Sep 2018, 123 pts with mCRPC and DRD were enrolled, of whom 39 had biallelic DRD (23 BRCA1/2). The median follow-up was 5.7 mo (2.0–23.7). Table depicts RRs for pts with biallelic DRD by BRCA status. Composite and objective RRs were 65% and 38% in pts with biallelic BRCA1/2, respectively. 3/8 pts (38% [2/5 BRCA1/2 and 1/3 non-BRCA]) with measurable visceral metastases showed objective response. Among the 20 biallelic responders, the duration of treatment (tx) has exceeded 4 mo in 13 pts and 6 mo in 8 pts; 14 pts remain on tx. The most common grade 3/4 hematologic AEs were anemia (25%) and thrombocytopenia (15%) (manageable by dose reduction/interruption). The most common grade 3/4 nonhematologic AEs were asthenia (6%) and hypertension (5%). Conclusions: These results suggest niraparib has compelling activity as monotherapy for pts with treatment-resistant mCRPC, particularly those with biallelic BRCA1/2 identified by a blood assay. Clinical trial information: NCT02854436. [Table: see text]
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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 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".