A Phase 1b/2 Study of Alpelisib in Combination with Cetuximab in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Why this work is in the frame
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Bibliographic record
Abstract
BACKGROUND: Alpelisib in combination with cetuximab showed synergistic anti-tumour activity in head and neck squamous cell carcinoma (HNSCC) models. OBJECTIVES: The recommended phase 2 dose (RP2D) was determined in a phase 1b dose-escalation study. Phase 2 evaluated anti-tumour activity with a randomised part in cetuximab-naïve patients and a non-randomised part in cetuximab-resistant patients. PATIENTS AND METHODS: Alpelisib was administered in 28 d cycles as whole tablets, suspension from crushed tablets or suspension from dispersible tablets in patients with platinum-resistant, recurrent/metastatic HNSCC. RESULTS: The RP2D determined for alpelisib was 300 mg/d. Alpelisib-cetuximab achieved an overall response rate of 25% and 9.9% and disease control rate of 75% and 43.7% in phase 1b and phase 2 studies, respectively. Median progression-free survival (PFS) per central review was 86 d for combination treatment and 87 d for cetuximab monotherapy (unadjusted HR 1.12; 95% CI 0.69-1.82; P > 0.05). When adjusted for baseline covariates [sum of longest diameters from central data, haemoglobin and white blood cell (WBC), the results favoured combination treatment (adjusted HR 0.54; 95% CI 0.30-0.97; P = 0.039). PFS per investigator assessment resulted in an unadjusted HR of 0.76 (95% CI 0.49-1.19; P > 0.05) favouring combination treatment. The median PFS in cetuximab-resistant patients was 3.9 months. CONCLUSIONS: The addition of alpelisib to cetuximab did not demonstrate a PFS benefit in cetuximab-naïve patients with advanced HNSCC. The alpelisib-cetuximab combination showed moderate activity in cetuximab-resistant patients, with a consistent safety profile. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01602315; EudraCT 2011-006017-34.
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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 | 0.001 |
| 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 it