Canadian Cancer Trials Group (CCTG) IND.234/223: PC_BETS (Prostate Cancer Biomarker Enrichment and Treatment Selection)–A molecularly selected cooperative group platform study.
Bibliographic record
Abstract
5066 Background: PC-BETS registered patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) for circulating tumour (ct)DNA-based genomic screening to biomarker select and stratify pts for enrolment in a multi-arm platform trial testing clinical activity of investigational therapies. Methods: Pts (≥ 18 years old, ECOG PS 0-1, life expectancy ≥ 6 months) had mCRPC, disease progression (PD), no CNS involvement or serious illnesses and had received AR pathway inhibitor therapy +/- chemotherapy. Eligible pts were registered and screened using plasma ctDNA and enrolled to a substudy (SS) based on the presence (or absence) of a prespecified biomarker (BM), using a prespecified algorithm and a virtual web-based Molecular Tumour Board (MTB). ctDNA testing used an established targeted sequencing approach customised for mCRPC. Pts without BM positive genomic alteration(s) for an open SS were randomized to a BM negative SS cohort; pts who were never enrolled were followed for outcomes. Pts without detected ctDNA were not eligible for enrolment but could be rescreened after >8 weeks. Pts who discontinued a SS could be rescreened. Primary endpoint was clinical benefit rate (CBR; PSA50 response, RECIST CR/PR, or SD ≥12 weeks). Eight SS opened between 2017-2020. Results: From 2017-2024, 568 pts were screened from 11 centres across Canada. Pts: median age 71.5 (range 47.7-94.7), prior chemotherapy in 47.0%, and median ctDNA fraction was 7%. 216 pts were enrolled to 1 or more SS (3 pts enrolled to >1). See Table for summary of results. For all SS, toxicities were as expected. In SS-E, 1 pt had CBR and 1 pt received 25 cycles but did not meet CBR (both pts had AKT mutations). Clinical and genomic correlations will be presented. SS C, F and G are reported separately. Conclusions: Biomarker selected platform designs are an efficient way to screen potential new therapeutics, are well suited to multi-centre cooperative group settings and are strongly supported by patients advocates. CBRs were not reported for SS 223, B and D while modest clinical activity was seen for SS A (in the BM- cohort only) and E. Clinical trial information: NCT03385655 . Total Screens / N pts 606 / 565 ctDNA+ screen / pts 443 / 426 N pts enrolled to SS 216 SS 223 A B C D E F G Drug/s Palbociclib Adavosertib Savolitinib Darolutamide CFI-40095 Ipatasertib Durvalumab / tremelimumab Carboplatin Target/pathway CDK 1 BRCA/ATM 2 MET AR PTEN PIK3CA/AKT TMB high BRCA/ATM 2 Drug supplied by Pfizer AstraZeneca Bayer 3 Treadwell Hoffman-La Roche 3 AstraZeneca 3 - Enrolled to SS(BM+/-) 19 (9/10) 25 (11/14) 16 (6/10) 72 (53/19) 18 (9/9) 8(BM+) 25 (15/10) 35(18/17) CBR (BM+) 0 0 0 0 1 CBR (BM-) 0 3 0 0 1 CDK4/6/CCND1 amplification or CDK12 mutations; 2 or other HRR-related defects; 3 Plus partial funding to support SS.
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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.015 | 0.002 |
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".