Phase I study of OGX-011, a second generation antisense oligonucleotide (ASO) to clusterin, combined with cisplatin and gemcitabine as first-line treatment for patients with stage IIB/IV non-small cell lung cancer (NSCLC)
Bibliographic record
Abstract
17078 Background: The clusterin gene is frequently expressed in NSCLC and encodes a cytoprotective chaperone protein that promotes cell survival and is upregulated in response to apoptotic stimuli such as chemotherapy. OGX-011 is an ASO that binds to clusterin mRNA thus potently regulating expression and chemosensitizing cancer cells. Previous Phase I studies of OGX-011 identified biologically active doses of 480mg to 640mg. The objective of this multi-center Phase I study was to define the Phase 2 dose of OGX-011 in combination with standard chemotherapy. Methods: Patients (pts) with chemotherapy-naive advanced stage IIIB/IV NSCLC were potentially eligible. OGX-011 is given as a 2hr IV infusion weekly after 3 loading doses (days -7, -5, and -3). OGX-011 dose escalation was planned to a maximum of 640mg. Cisplatin was given at 75 mg/m 2 IV day 1 and gemcitabine 1250mg/m 2 IV days 1 and 8, on a 21-day schedule up to 6 cycles. Pharmacokinetic profiling was done in cycle 1. Results: Between Jan 2004 and Apr 2005, 10 patients were enrolled. Median age 62 yrs (49–75); 4 female. ECOG 0/1: 3/7. Stage IIIB/IV: 1/9. 9 of 10 pts completed at least one cycle; 1 withdrew after one dose of OGX-011 due to progressive disease (PD). Of the 9 pts, 6 received ≥ 5 cycles and 3 received 2–4 cycles (2 patients discontinued due to PD and 1 at the pts request). Median follow-up: 5.0m (1.6 - 6.7m). As of Jan 2006, 2 pts had a PR; 5 had SD; 2 had PD. 4 pts had 5 serious adverse events: elevated creatinine, hypoxia, pneumonia, pleural effusion, and febrile neutropenia. 3 pts had Gr 3 hyponatremia. Gr 3/4 hematological toxicities in 10–40% and 10–20%, respectively. No dose-limiting toxicities noted; 7 pts received OGX-011 at 640 mg. A proportional increase in OGX-011exposure (C max and AUC 0-inf ) from 480 to the 640 mg was noted with no apparent effect on GEM/CIS. Conclusions: OGX-011 was well tolerated and can be given at biologically active doses (640 mg) with standard GEM/CIS chemotherapy for patients with advanced NSCLC. A multicenter Phase II trial of this combination is underway. Sponsored by OncoGenex Technologies, Inc. with Isis Pharmaceuticals Inc. [Table: see text]
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".