A phase I study of enfortumab vedotin (ASG-22CE; ASG-22ME): Updated analysis of patients with metastatic urothelial cancer.
Bibliographic record
Abstract
106 Background: Enfortumab vedotin, an antibody–drug conjugate, delivers monomethyl auristatin E to tumors expressing Nectin-4, which is overexpressed in metastatic urothelial cancer (mUC). Methods: This Phase I study (NCT02091999) enrolled patients (pts) with solid tumors, including pts with mUC, treated with ≥1 prior chemotherapy regimen. All pts received different dose levels of IV enfortumab vedotin (0.5, 0.75, 1, 1.25 mg/kg) once weekly for 3 out of 4 wks. Nectin-4 expression was determined by IHC on archival tumor specimens and quantified by histochemical scoring (H-score). Primary endpoint was tolerability; secondary endpoint was antitumor activity assessed every 8 wks per RECIST v1.1. Results: As of 3 Jan 2017, 68 pts with mUC (46 M/22 F; median age, 67 yr [range: 41–84]) had been treated. Of these, 62% received ≥2 prior therapies in the metastatic setting and 40% had prior immune checkpoint inhibitor (CPI) therapy. In these pts, Nectin-4 expression was high and prevalent (median H-score, 280 [range: 32–300]). Treatment-related adverse events (TRAEs) were reported in 58 pts (85%); diarrhea, fatigue, nausea, and pruritus were TRAEs reported in ≥25% of pts. Most TRAEs were grade ≤2 in severity; 19 pts (28%) experienced a TRAE of grade ≥3. The most common grade ≥3 AEs (occurring in ≥5 pts), regardless of attribution to treatment, were urinary tract infection (10%) and hypophosphatemia (9%). No treatment-related deaths have occurred. Sixty pts had ≥1 post-baseline assessment. Antitumor activity was observed across the dose range; overall response rate (ORR) was 40% (95% CI: 27.6–53.5) for all evaluable pts (n = 60), 46% (95% CI: 25.6–67.2) in pts with prior CPI exposure (n = 24), and 44% (95% CI: 19.8–70.1) in pts with metastasis to the liver (n = 16). Complete responses were noted in 3 pts at doses ≥1 mg/kg. Median treatment duration was 26 wks (range: 5.1–64.6), median duration of response was 18 wks (95% CI: 8.4–40.1), and median progression-free survival was 17 wks (95% CI: 15.1–23.3). Study enrollment is ongoing. Conclusions: Enfortumab vedotin demonstrated a favorable tolerability profile with encouraging antitumor activity in heavily pretreated mUC, including pts for whom CPIs have failed. Clinical trial information: NCT02091999.
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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 | 0.002 | 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 | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".