The CCTG CO.26 trial: A phase II randomized study of durvalumab plustremelimumab and best supportive care (BSC) vs BSC alone in patients with advanced colorectal carcinoma (CRC) refractory to standard therapies.
Bibliographic record
Abstract
TPS3621 Background: Durvalumab (D) is a human monoclonal antibody (mAb) that inhibits binding of programmed cell death ligand 1 (PD-L1) to its receptor (PD-1) thereby preventing reduction in the number and efficacy of activated T-cells. Tremelimumab is a mAb directed against the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) thereby resulting in enhanced T-cell activation and anti-tumour activity. Monotherapy with the anti-PD-1 agent pembrolizumab has demonstrated significant activity in CRC pts with tumours demonstrating microsatellite instability (MSI-H). Inhibiting PD-1/PD-L1 alone is likely of limited benefit in advanced CRC as only 5% of pts are MSI-H. Targeting both PD-L1 and CTLA-4 may have additive or synergistic activity as the mechanisms of action of CTLA-4 and PD-L1 inhibition are non-redundant. This study is designed to evaluate whether combining PD-L1 and CTLA-4 inhibition will lead to improved patient survival vs BSC alone in advanced CRC, regardless of MSI status. Methods: This randomized phase II study (ClinicalTrials.gov NCT02870920) will assess the efficacy and safety of D+T vs BSC in pts with metastatic or advanced, unresectable, refractory CRC (n = 180). Pts have failed standard chemotherapy based regimens containing a fluoropyrimidine, irinotecan and oxaliplatin (and an EGFR inhibitor, if Ras wild type) and no other therapeutic options. Pts are randomized in a 2:1 ratio to receive D (1500 mg) D1 q 28 days and T (75 mg) D1 for first 4 cycles. Treatment will continue until disease progression, death, intolerable toxicity, or patient/investigator decision to stop. Primary endpoint is overall survival; secondary endpoints include progression free survival, safety, overall response rate and quality of life. Analysis will be according to randomized group stratified by ECOG PS (0 vs 1) and site of tumour (right vs transverse vs left vs rectum). In addition, blood, plasma, and archival tissue will be collected and assessed for potential prognostic and predictive biomarkers, including tumour MSI status. As of February 1 2017, 20 pts have been randomized and recruitment is ongoing. Clinical trial information: NCT02870920.
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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) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.009 | 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".