A phase I study of the humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) TheraCIM-h-R3 (nimotuzumab) in patients with advanced solid tumors
Bibliographic record
Abstract
13054 Background: Nimotuzumab is a humanized mAb against the extracellular ligand binding domain of EGFR. Although well tolerated when combined with radiotherapy in previous studies, the pharmacodynamics (PD) of nimotuzumab has not been elucidated. This phase I study was designed to evaluate the safety, tolerability and PD of nimotuzumab. Methods: Eligibility criteria included advanced solid tumors refractory to standard therapy and performance status of ECOG 0–2. Nimotuzumab was administered intravenously weekly × 6 and then every other week (6 weeks = 1 treatment cycle). Tumor and skin biopsies were obtained at baseline and after 2 weeks of treatment. Results: To date, 9 patients (7 m/2 f, median age 60, 7 colorectal cancer, ECOG 0:1:2 = 5:3:1, prior therapy 1:2:3+ = 1:3:5) have been treated on the first 2 dose levels (100 mg and 200 mg) for a total of 13 treatment cycles. The most common toxicities, mainly grade 1- 2, were lymphopenia (n = 8 patients), fatigue (n = 8), abnormal liver function tests (n = 7) and anemia (n = 6). Observed grade 3 toxicities include: pain (n = 3), hyponatremia (n = 2), elevated ALP (n = 2), fatigue (n = 1), hyperglycemia (n = 1) and hyperkalemia (n = 1). One patient at the first dose level experienced grade 3 fatigue, at least possibly attributable to nimotuzumab, and thus considered as a dose-limiting toxicity (DLT). No DLT were observed in the expanded cohort and dose level 2. No skin toxicities were observed. Stable disease was seen in 3 patients with colorectal cancer. PD from tumor and skin biopsies will be presented, and may clarify the reason for the lack of skin toxicity. Conclusions: Overall nimotuzumab was well tolerated, with disease stabilization observed in heavily pretreated patients. Accrual continues at dose level 3 (400 mg) with one further planned dose level (800 mg). [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) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".