BM-32 * CERITINIB (LDK378) FOR TREATMENT OF PATIENTS WITH ALK-REARRANGED (ALK+) NON-SMALL CELL LUNG CANCER (NSCLC) AND BRAIN METASTASES (BM) IN THE ASCEND-1 TRIAL
Bibliographic record
Abstract
BACKGROUND: Ceritinib is an ALK inhibitor (ALKi) recently approved for patients with ALK+ advanced NSCLC. Efficacy and safety were evaluated in a subset of patients with BM in the phase I ASCEND-1 study. In 246 patients with ALK+ NSCLC who received ceritinib 750 mg/day, overall response rate (ORR) was 58.5% (95% CI: 52.1, 64.8) and was 66.3% (55.1, 76.3) and 54.6% (46.6, 62.4) in ALKi-naïve and ALKi-treated patients, respectively. METHODS: Patients with ALK+ advanced NSCLC and clinically/neurologically stable BM at baseline who received ceritinib 750 mg/day were analyzed for response based on investigator assessment. RESULTS: Among 246 patients, 124 had BM at baseline, including 98 with prior ALKi treatment and 26 who were ALKi-naïve. The BM subset had a median age of 51.0 years; 85.5% with an ECOG PS ≤1; 58.1% Caucasian, 39.5% Asian; median time from NSCLC diagnosis to first ceritinib dose was 20.5 months. Median duration of exposure was 27 weeks. ORR was 54.0% (44.9, 63.0) in the full cohort [50.0% (39.7, 60.3) in ALKi-treated and 69.2% (48.2, 85.7) in ALKi-naïve]. Median DOR was 7.0 mo (5.5, 9.7) for the full subset [6.9 mo (4.8, 8.5) in ALKi-treated and not estimable (NE) in ALKi-naïve]. Median PFS was 6.9 mo (5.4, 8.4) [6.7 mo (4.9, 8.4) and 8.3 mo (4.6, NE) in ALKi-treated and ALKi-naïve]. Measurable target lesions were identified at baseline in 14 patients (10 ALKi-treated, 4 ALKi-naïve). Seven of these patients achieved a response in the brain (4 ALKi-treated, 3 ALKi-naïve) and 3 had stable disease (all ALKi-treated). The most common adverse events (all grades) in all patients and the BM subset were diarrhea (86% vs 79%), nausea (80% vs 82%), and vomiting (60% vs 63%). CONCLUSIONS: Ceritinib has clinically significant durable efficacy in patients with ALK+ NSCLC, including patients with BM, regardless of prior ALKi treatment.
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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 | 0.000 | 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 | 0.000 | 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".