Phase 1 first-in-human (FIH) study of nesvacumab (REGN910) a fully human and selective angiopoietin-2 (Ang2) monoclonal antibody (MAb): Results from hepatocellular carcinoma (HCC) cohort.
Bibliographic record
Abstract
2540 Background: Nesvacumab (N) is an Ang2 selective, human MAb that potently blocks signaling through the Tie2 receptor, inhibiting tumor angiogenesis and growth. In mouse xenograft models of human solid tumors, N inhibits tumor growth. In the dose-escalation (DE) portion of this trial [JCO 31, 2013 (suppl; abstr 2517)] anti-tumor activity (significant decline AFP) was observed in a patient (pt) with HCC, prompting expansion in this indication. Methods: Safety and anti-tumor activity are reported from all pts with HCC treated in the FIH trial in DE and expansion phases combined. In DE, single agent N was administered IV Q2W at 1 of 5 dose levels starting at 1 mg/kg; HCC expansion at 2 doses, 12, and 20 mg/kg Q2W, were studied. Results: 15 pts with HCC were enrolled: [11M/4F; median age 69 (range 24-82); ECOG PS 0=6/1=9; prior sorafenib 60%]. Dose levels were: 1 (n=1), 12 (n=6) and 20 mg/kg (n=8). Median number of doses administered was 8 (range 1-23). No pts experienced protocol defined DLTs. Most common adverse events (AEs) (all/related) were fatigue (8/5), diarrhea (5/0), decreased appetite (4/2), dizziness (4/0), nausea (4/2), abdominal pain (3/1), vomiting (3/1), back pain (3/0) and dyspnea (3/0); 9 grade ≥3 events reported in 7 pts, of which 3 events were assessed as treatment related: abdominal pain, infusion-related reaction, and retinal detachment, each reported in a single pt. One pt treated with 20 mg/kg experienced a non-severe lower GI bleed, assessed as not treatment related. No objective responses were observed. Two pts experienced a ≥ 50% decline in AFP (1 pt >90%). Nine of 15 pts achieved best response of SD (median duration 24 wks); 6 pts achieved SD for ≥ 20 wks. Notably, 5 of 8 pts treated at 20 mg/kg achieved best response of SD; median duration of 40 wks. Conclusions: Single-agent N up to 20mg/kg Q2W was generally tolerated in pts with HCC, with primarily mild and moderate AEs, independent of dose. SD occurred in 60% of pts across doses, with prolonged SD at highest dose. The safety profile supports combination with chemotherapy and/or other anti-angiogenic agents. Expansion in pts with HCC receiving N in addition to sorafenib is ongoing. Clinical trial information: NCT01271972.
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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 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".