Phase I trial of the programmed death receptor 1 (PD-1) inhibitor, BI 754091, in patients (pts) with advanced solid tumors.
Bibliographic record
Abstract
212 Background: Tumors may achieve immune evasion by expressing PD ligand-1 (PDL-1) to bind to PD-1 expressed on activated T cells, initiating immunosuppressive signals within the tumor. Pro-inflammatory anti-tumor activity can be restored when this interaction is blocked by therapeutic PD-1 or PDL-1 inhibition. BI 754091 is a monoclonal IgG4Pro antibody directed against PD-1 that has demonstrated anti-tumor activity in vitro and in vivo. We present the results of the first in human study evaluating BI 754091 in patients with advanced solid tumors. Methods: Patients who had exhausted standard treatment (tx) options, including prior anti-PD-1 tx, were enrolled to receive BI 754091 IV every 3 weeks (Q3W) in one of 3 sequential dose escalation cohorts (80, 240 and 400 mg), 3 patients/cohort, to evaluate the safety and tolerability and establish the maximum-tolerated dose (MTD) or recommended Phase II Dose (RPIID). Additional anti-PD-1 naïve patients with select solid tumors are being enrolled in dose expansion to be treated with the selected RPIID. The objectives of the dose expansion cohort are to evaluate the safety, tolerability, PK and preliminary efficacy of the RPIID of BI 754091, in patients with advanced solid tumors. Results: 17 patients have enrolled to date, 9 patients in the dose escalation and 8 patients in the dose expansion cohorts. Both, safety and PK profile supported a RPIID of 240 mg. The most common all grade Treatment Related Adverse Events (TRAE) were fatigue 35% (6 patients), decreased appetite 18% (3 patients) and arthralgia 12% (2 patients). There were no dose-limiting toxicities, tx-related serious adverse events, or TRAEs ≥Grade 3 reported. To date, one patient (gastric cancer) has had a partial response, 8 had stable disease, and 8 patients continue on treatment. Additional efficacy data among patients in dose-expansion will be reported. Conclusions: BI 754091 is safe and well-tolerated across all dose levels tested for advanced solid tumors, with preliminary evidence of activity. A dose of 240 mg Q3W was selected for dose expansion and RPIID based upon the available safety and PK data. Clinical trial information: NCT02952248.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| 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 | 0.003 |
| 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".