The AfFIRM Study: A multicenter phase 2 study of single-agent filanesib (ARRY-520) in patients with advanced multiple myeloma.
Bibliographic record
Abstract
TPS8613 Background: An unmet medical need exists for patients (pts) with multiple myeloma (MM) whose disease has progressed despite prior exposure to immunomodulatory agents (IMiDs) and proteasome inhibitors (PIs), particularly if their disease has become refractory to carfilzomib (CFZ) and/or pomalidomide (POM). Filanesib is a highly selective, targeted kinesin spindle protein (KSP) inhibitor that has shown promising activity and a manageable safety profile as a single agent in heavily pretreated pts with MM. Due to a distinct mechanism of action, filanesib is expected to be active in cells that have become resistant to IMiDs and PIs, potentially addressing a significant unmet need in the treatment of patients with refractory MM. Nonclinical and prior clinical data have suggested that pts with high serum levels of α 1-acid glycoprotein (AAG) may not obtain therapeutic benefit from filanesib as a result of decreased unbound fraction of drug and ineffective therapeutic exposure. The correlation between Baseline AAG and clinical response to single-agent filanesib will be evaluated. Methods: This single-arm Phase 2 study is designed to assess the efficacy and safety of single-agent filanesib in ~160 pts with MM at centers in North America and Europe (NCT02092922). Eligible pts have received at least 2 prior lines of therapy; have received prior bortezomib and lenalidomide; and have disease refractory to CFZ and/or POM. Filanesib (1.50 mg/m2/day) is administered intravenously on Days 1, 2, 15 and 16 in continuous 28-day cycles with prophylactic filgrastim until disease progression or unacceptable toxicity. Objective response is assessed by independent central review and classified per International Myeloma Working Group (IMWG) criteria. AAG is measured by a central laboratory using a validated immunoturbidimetric assay. The primary endpoint is objective response rate (ORR) in pts with low Baseline AAG. Secondary endpoints are ORR in pts with high Baseline AAG, duration of response, time to best response, clinical benefit rate, disease control rate, progression-free survival, time to next treatment, overall survival and safety. The study includes a 25-pt pharmacokinetics/QT substudy. Clinical trial information: NCT02092922.
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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) | 0.001 | 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 | 0.001 |
| 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".