A phase I study of BMS-936558 in combination with gemcitabine/cisplatin, pemetrexed/cisplatin, or carboplatin/paclitaxel in patients with treatment-naive, stage IIIB/IV non-small-cell lung cancer.
Bibliographic record
Abstract
TPS2615 Background: Lung cancer is the leading cause of cancer-related mortality worldwide and non-small-cell lung cancer (NSCLC) accounts for ~85% of all cases. Platinum-based chemotherapy alone or in combination with bevacizumab is considered first-line standard of care for advanced NSCLC. Despite such therapy, most patients (pts) will experience disease progression within 6 months and die from their disease within 1 year. Programmed death-1 (PD-1) is a coinhibitory receptor that negatively regulates T-cell activation; PD-1 expression by tumor infiltrating lymphocytes is associated with poor prognosis in NSCLC. BMS-936558 is a fully human anti-PD-1 monoclonal antibody that blocks ligand interaction with PD-L1 and PD-L2. In a phase 1 trial, BMS-936558 had antitumor activity at doses of 1-10 mg/kg in pts with advanced tumors, and impressive tumor responses in heavily pre-treated pts with NSCLC. Here we describe a phase 1 study planned to evaluate the safety and tolerability of BMS-936558 in combination with 3 standard, platinum-based doublet chemotherapy regimens in pts with NSCLC. Methods: Treatment-naïve pts with stage IIIB/IV NSCLC will be enrolled. Treatment arms will include: A) gemcitabine 1250 mg/M2 on day 1 (D1) and day 8 (D8)/cisplatin 75 mg/M2 D1/BMS-936558 D1; B) pemetrexed 500 mg/M2 D1/cisplatin 75 mg/M2 D1/BMS-936558 D1; and C) carboplatin AUC 6 D1/paclitaxel 200 mg/M2 D1/BMS-936558 D1. The starting dose of BMS-936558 will be 10 mg/kg for each treatment arm. A decision to de-escalate to a lower dose (2 or 0.3 mg/kg) will be guided by the number of dose-limiting toxicities reported per treatment arm. Chemotherapy will be given for 4 cycles (1 cycle = 3 weeks). BMS-936558 will be administered every 3 weeks until disease progression, intolerable toxicity, or withdrawal of consent. The primary objectives are to assess safety and tolerability by measuring the frequency of adverse events (AEs), serious AEs, and laboratory abnormalities; secondary objectives are to determine the overall response rate and disease control rates based on RECIST 1.1. As of February 1, 2012, 2 patients were enrolled.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".