A phase I trial of BI 754091, a programmed death receptor 1 (PD-1) inhibitor, in patients with advanced solid tumors
Bibliographic record
Abstract
Background: Tumors can evade immune responses through expression of PD ligand 1 (PD-L1), which, upon binding to PD-1 on activated T-cells, initiates immunosuppressive signals in the tumor. Therapeutic PD-1 or PD-L1 inhibition can block this interaction and restore pro-inflammatory anti-tumor activity. BI 754091 is a monoclonal IgG4Pro antibody inhibitor of PD-1 with proven in vitro and in vivo anti-tumor activity. In this first-in-human study, we evaluate BI 754091 in patients (pts) with advanced solid tumors. Methods: Eligible pts had exhausted standard treatment (tx) options, including prior anti-PD-1 tx. Pts received BI 754091 IV every 3 weeks (Q3W) in one of three sequential dose escalation cohorts (80, 240 and 400 mg; 3 pts/cohort) to assess the safety and tolerability, and determine the maximum-tolerated dose/recommended Phase II dose (RP2D). Additional anti-PD-1 naïve pts with certain solid tumors are also being enrolled for dose expansion, to be treated at the RP2D. The objectives of the dose expansion phase are to assess the safety, tolerability, pharmacokinetics (PK) and preliminary efficacy of BI 754091 at the RP2D in this setting. Results: 35 pts have enrolled as of 19 Feb 2018 (dose escalation, n = 9; dose expansion, n = 26). Safety and PK profiles supported a RP2D of 240 mg Q3W. The most common all-grade tx-related adverse events (TRAEs) were fatigue (31%; 11 pts) and decreased appetite (14%; 5 pts). No dose-limiting toxicities or tx-related serious AEs were reported. 1 pt had a Grade 3 TRAE (AST elevated). To date, 4 pts have had a confirmed (gastric/ovarian/breast cancer) or unconfirmed (renal cancer) partial response and 16 had stable disease. 8 pts continue on tx. Further efficacy data from the dose-expansion cohort will be reported. Conclusions: BI 754091 was well tolerated at all doses tested for advanced solid tumors, with preliminary evidence of activity. Based on the available safety and PK data, the RP2D for dose expansion was 240 mg Q3W.
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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 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".