Mature results from EV-101: A phase I study of enfortumab vedotin in patients with metastatic urothelial cancer (mUC).
Bibliographic record
Abstract
377 Background: Enfortumab vedotin (EV) is an antibodydrug conjugate that delivers MMAE, a microtubule disrupting agent, to tumors expressing Nectin-4, a protein found on most urothelial cancers. Preliminary results of the EV-101 study (NCT02091999) suggest EV is active and tolerable. Methods: Patients with mUC treated with ≥1 prior chemotherapy, or those ineligible for cisplatin, received EV 1.25 mg/kg on Day 1, 8, and 15 every 28 day cycle. The primary objective was tolerability; antitumor activity (ORR per RECIST v1.1), assessed every 8 wk, was a secondary objective. Results: As of14 Sept 2018,112 pts with mUC received EV with a median follow up of 13.4 mo. Bladder was the primary tumor site in 86 pts (77%) and 33 (29.5%) had liver metastases (LM). Nearly all pts received prior platinum chemotherapy; 89 (79.5%) received prior anti-PD(L)1. EV was well tolerated; fatigue (53%), alopecia (46%), and decreased appetite (42%) were the most commonly reported treatment-related AEs (TRAEs). Anemia (8%), hyponatremia (7%), UTI (7%), and hyperglycemia (6%) were the grade ≥3 AEs reported in ≥5% of pts regardless of attribution; 4 fatal TRAEs were reported (respiratory failure, urinary tract obstruction, diabetic ketoacidosis, multi-organ failure). Confirmed ORR was 42% (CR, n = 5; PR, n = 42). Among responders, median duration of response was 7.7 mo (95% CI 5.6, 9.6) and 23.4% of responses were ongoing with a median follow up of 11.3 mo. Estimated median PFS and OS were 5.4 mo (95% CI 5.1, 6.3) and 12.5 mo (95% CI 9.3, 16.1), respectively; OS at 1 yr was 51.8%. Similar results were seen in pts with prior anti-PD(L)1 and with LM (Table). Conclusions: Single-agent EV was generally well tolerated and provided encouraging response and survival data in a population with an unmet medical need including pts with LM, which is associated with poor prognosis. Phase 2 and 3 monotherapy studies as well as evaluation of combination therapies are ongoing. Clinical trial information: NCT02091999. [Table: see text]
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".