A phase I/II study of CR011-vcMMAE, an antibody-drug conjugate, in patients (pts) with locally advanced or metastatic breast cancer (MBC)
Bibliographic record
Abstract
1067 Background: Glycoprotein NMB (GPNMB), also known as osteoactivin, has been shown to regulate metastasis of breast cancer in vivo. CR011-vcMMAE, a fully-human monoclonal anti-GPNMB antibody conjugated to the tubulin inhibitor monomethylauristatin E, is safe and active in pts with advanced melanoma. This is the first study of CR011-vcMMAE in breast cancer. Methods: Eligible pts with MBC had ≥ 2 prior chemotherapy regimens, including a taxane, an anthracycline, and capecitabine; and ECOG PS ≤ 2. Doses were escalated to 1.88 mg/kg IV q3w (the maximum tolerated dose [MTD] in melanoma) using a standard 3+3 design. Immunohistochemistry (IHC) with goat polyclonal antibody to GPNMB was performed on pt biopsy specimens and on tissue microarrays containing normal breast, DCIS, breast tumor and lymph node metastases. Results: 10 pts with MBC (median age 57, range 36 - 69) had a median of 7 prior regimens and were treated with CR011-vcMMAE for a median of 2 cycles (range 1–4). In the first 2 pts at 1.34 mg/kg, dose limiting toxicity of worsening peripheral sensory neuropathy was observed. Pts with baseline neuropathy worse than grade 1 were subsequently excluded. Pts were treated at 1.0 mg/kg (n = 3), 1.34 mg/kg (n = 5), and 1.88 mg/kg (n = 2); enrollment at 1.88 mg/kg is continuing. Other adverse events (AEs) were grade 1/2 anorexia and pain in 4 pts; diarrhea, rash, fatigue, and neuropathy in 3 pts; and grade 3 rash in 1 pt. Evidence of antitumor activity has been observed. A response of 37% tumor shrinkage was seen in a pt after only 2 cycles and is ongoing. A second pt had a 51% reduction after 2 cycles, but had PD after 12 weeks. Breast tumor samples were more likely to stain positive for GPNMB than normal breast tissues. Conclusions: CR011-vcMMAE 1.34 mg/kg IV q3w is well-tolerated in heavily pretreated pts with MBC. The 1.88 mg/kg q3w dose is being assessed and phase II expansion is planned at the MTD. IHC of pt tumor specimens is being evaluated. [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 | 0.001 |
| 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 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| 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".