ROAR: a phase 2, open-label study in patients (pts) with BRAF V600E–mutated rare cancers to investigate the efficacy and safety of dabrafenib (D) and trametinib (T) combination therapy.
Bibliographic record
Abstract
TPS2604 Background: Combination D + T is approved for the treatment of BRAF V600E/K–mutant unresectable or metastatic melanoma. BRAF V600E mutations have also been identified in some rare cancers, including anaplastic thyroid cancer, biliary tract cancer, gastrointestinal stromal tumor, nonseminomatous germ cell tumor, hairy cell leukemia (HCL), World Health Organization (WHO) grade I/II glioma, WHO grade III/IV glioma, multiple myeloma, and adenocarcinoma of the small intestine. US incidence rates of these rare tumors range from 0.07 to 6.3 per 100,000, with BRAF V600E mutation frequency ranging from 3% in high-grade glioma to 90% in HCL. Therefore, the ROAR study is underway in pts with these 9 rare BRAF-mutant cancers to assess the safety and efficacy of D + T combination therapy. Methods: This international, multicenter, open-label phase 2 study (NCT02034110) uses a Bayesian hierarchical statistical design that increases study power by borrowing information across histology cohorts based on the emerging response rate. Enrollment for each of the 9 cohorts (up to 25 pts each) may be stopped early for futility or efficacy if various criteria occur based on accrued data. Pts with BRAF V600E–mutant histologically or cytologically confirmed advanced disease with no available standard treatment options are eligible. Enrollment based on local BRAF V600E mutation results is permitted. Pts receive D (150 mg twice daily orally) and T (2 mg once daily orally) on a continuous dosing schedule until unacceptable toxicity, disease progression, or death occurs. Responses are assessed every 8 weeks per tumor-specific response criteria while pts are on study treatment. The primary study endpoint is overall response rate by investigator assessment. Secondary objectives include duration of response, progression-free survival, overall survival, and safety. Pharmacodynamic markers and quality of life will also be evaluated. If a histological cohort meets stopping criteria for early efficacy, an expansion cohort will be opened. This ongoing trial is currently recruiting pts at 48 centers in the United States, Canada, Europe, and South Korea. Clinical trial information: NCT02034110.
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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 | 0.003 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.004 |
| Insufficient payload (model declined to judge) | 0.005 | 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".