A phase I study of nivolumab (anti-PD-1; BMS-936558, ONO-4538) plus platinum-based doublet chemotherapy (PT-doublet) in chemotherapy-naive non-small cell lung cancer (NSCLC) patients (pts).
Bibliographic record
Abstract
8072 Background: A phase I study ofnivolumab (a PD-1 receptor blocking Ab) demonstrated durable responses and a tolerable safety profile in NSCLC pts who failed ≥1 chemotherapy regimen. We report an interim analysis of a phase I study with nivolumab + PT-doublets in chemotherapy-naive advanced NSCLC pts. Methods: Stage IIIB/IV NSCLC pts were randomized by histology ≥9 wk prior to data lock (Dec 2012) to: A) nivolumab/gemcitabine/cisplatin; B) nivolumab/pemetrexed/cisplatin; or C) nivolumab/carboplatin/paclitaxel according to a phase I dose de-escalation design to assess the toxicities and incidence of DLTs in the first 6 wk of dosing. Nivolumab doses were started at 10 mg/kg IV Q3W and given until progression. PT-doublet was given for 4 cycles at standard dosing. At a tolerable dose, cohorts were expanded up to 20 pts. Results: 43 pts were treated with nivolumab + PT-doublet: Arm A, n=12 squamous (sq); Arm B, n=15 (non-sq); and Arm C, n=16 (3 sq + 13 non-sq). No DLTs were seen across arms. Gr 3-4 regimen-related AEs were 49% across arms, and 25%, 47%, and 69% for Arms A, B, and C, respectively. Select Gr 3-4 toxicities reported included: pneumonitis, rash, nephritis, and colitis (Table). 3 pts had Gr 3 pneumonitis and were addressed with management algorithms (dose discontinuation and immune-modulating therapies). 2 pts fully resolved, however 1 resolved pt subsequently died from Aspergillus pneumonia. 1 pt died of disease progression with unresolved pneumonitis (autopsy confirmed). Total/Confirmed ORRs (RECIST 1.1) were 43/33%, 40/33%, and 31/31% in Arms A, B, and C, respectively. Conclusions: No DLTs were seen with 10 mg/kg nivolumab combined with PT-doublets; maintenance treatment is ongoing. Similar to monotherapy, select nivolumab related toxicities can be addressed with management algorithms. Safety, durability, and confirmation of responses will be updated based on a 2013 data analysis, including a 5 mg/kg nivolumab dose cohort. Clinical trial information: NCT01454102. [Table: see text]
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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".