Safety and clinical activity of first-line durvalumab in advanced NSCLC: Updated results from a Phase 1/2 study.
Bibliographic record
Abstract
e20504 Background: Single-agent durvalumab demonstrated manageable safety and encouraging clinical activity in advanced squamous and non-squamous NSCLC in preliminary analyses from the Phase 1/2 1108 study (NCT01693562). Here we present updated safety data and clinical activity in NSCLC pts with no prior treatment for advanced disease. Methods: In this Phase 1/2 dose-escalation and expansion study, pts with Stage IIIB/IV NSCLC, ECOG PS 0–1, and availability of a fresh tumor biopsy and/or archival tumor tissue for PD-L1 testing received durvalumab 10 mg/kg every 2 weeks for up to 12 months, with retreatment permitted for those progressing after 12 months of therapy. Tumor PD-L1 expression was assessed using the Ventana PD-L1 (SP263) Assay (PD-L1 high: ≥25% of tumor cells with membrane staining). Results: As of 24 October 2016, 59 pts (63% ECOG PS 1, 49% squamous) received first-line durvalumab. Median duration of follow-up was 17.3 (1.0–36.8) mos. Safety profile was consistent with the overall (N = 304, ≥0 prior lines of therapy) NSCLC cohort. All-grade treatment-related adverse events (AEs) were reported in 56%; the most common were fatigue (15%), diarrhea (13%), and decreased appetite (10%). 7% had a treatment-related AE leading to discontinuation of durvalumab, including diarrhea in 2 pts. Grade ≥3 treatment-related AEs (all n = 1) occurred in 10%; 1 pt died due to drug-related pneumonia. 49 pts had high PD-L1 expression and 9 pts had low/negative PD-L1 expression; data are not summarized for the latter group due to the small number of pts. For the PD-L1 high subpopulation, confirmed ORR (investigator-assessed RECIST v1.1) was 28.6% (95% CI 16.6–43.3) and disease control rate (stable disease ≥24 weeks) was 42.9% (95% CI 28.8–57.8); median PFS was 4.0 months (95% CI 2.3–9.1), median OS was 21.0 months (95% CI 14.5–not estimable), and 12-month OS rate was 72% (95% CI 56–83). Response rates were similar and durable regardless of histology. Conclusions: Consistent with prior data, durvalumab had a tolerable safety profile in advanced treatment-naïve NSCLC. Clinical activity was seen in PD-L1 high pts, with encouraging OS. Clinical trial information: NCT01693562.
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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 | 0.003 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 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".