MGCD265, a multitargeted oral tyrosine kinase receptor inhibitor of Met and VEGFR, in combination with docetaxel.
Bibliographic record
Abstract
e13604 Background: MGCD265 is a multi-target oral tyrosine kinase receptor inhibitor that targets Met, VEGFRs 1, 2, 3, Tie and Ron. The maximum tolerated dose (MTD) of MGCD265 in combination with docetaxel was initially determined using micronized tablets. MGCD265 formulation was improved and the MTD of MGCD265 in combination with docetaxel using the updated formulation was re-evaluated. Methods: Patients (pts) with metastatic or advanced solid tumors were enrolled in this Phase I, open-label, dose-escalating study to assess safety, pharmacodynamics (PD) and pharmacokinetics (PK) as well as anti-tumor activity of the combination. MGCD265 was administered every day over a 3-week cycle and docetaxel (50 then 75 mg/m2) was given intravenously once every 3 weeks (q3w). Results: As of January 11, 2012, 34 pts were enrolled (M/F: 19/15; ECOG 0/1: 19/15; median age: 64 years old). The MTD of the combination was initially defined as MGCD265 (72 mg/m2 BID)+docetaxel (75 mg/m2 q3w) based on the occurrence of dose limiting toxicities (DLTs) in 2 pts who were treated with MGCD265 at 96 mg/m2 BID (fatigue in 1 pt and diarrhea & lipase elevation in the other pt). The updated formulation of MGCD265 was introduced at 48 mg/m2 BID (n=3) with dose escalation to 72 mg/m2 BID (n=3) and 96 mg/m2 (n=4) with no observed DLTs, though the exposure of the two formulations were generally comparable. Overall, objective partial responses (per RECIST 1.1) were observed in 2/9 pts with NSCLC, 1/3 pts with prostate cancer and 1/1 pt with endometrial cancer. Stable disease for 6 cycles or more was observed in 6 pts. Treatment-related ≥ grade 3 toxicity reported in ≥ 2 pts were neutropenia, leukopenia, diarrhea and elevated lipase. The PD profile indicated an increase in the plasma level of VEGF and a decrease in plasma level of HGF at Cycle 1 Day 8 compared to baseline in some patients. Conclusions: MGCD265 was found to be well tolerated using the updated formulation in combination with full-dose docetaxel. Anti-cancer activity, supporting Phase II development of the combination, was observed.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".