Phase I study of BI 754111 (anti-LAG-3) plus BI 754091(anti-PD-1) in patients (pts) with advanced solid cancers, followed by expansion in pts with microsatellite stable metastatic colorectal cancer (mCRC), anti-PD-(L)1-pretreated non-small cell lung cancer (NSCLC) and other solid tumors
Bibliographic record
Abstract
Background: Lymphocyte-activation gene 3 (LAG-3) is a negative regulator of immune response implicated in T cell exhaustion and tumor immune escape. Available data demonstrate that tumor-derived T cells frequently co-express the PD-1 and LAG-3 co-inhibitory receptors and that dual blockade of the LAG-3 and PD-1 pathways results in more potent reactivation of T-cell function and anti-tumor immune response than blockade of the individual pathway. BI 754091 and BI 754111 are monoclonal IgG4Pro antibodies (mAbs) against PD-1 and LAG-3, respectively. In this Phase I study, we investigate the safety, tolerability, PK, and preliminary efficacy of the combination of these 2 mAbs. Trial design: This 2-part, open-labeled, non-randomized ongoing study consists of dose escalation in pts with advanced solid tumors followed by expansion cohorts in pts with NSCLC, microsatellite stable (MSS) mCRC, or any PD-1/PD-L1 pretreated solid tumor with high tumor mutational burden (TMB-H) and/or high microsatellite instability and/or DNA mismatch repair deficiency (MSI-H/MMRd). Dose escalation in pts with solid tumors started at 4mg q3w BI 754111 and was guided by Bayesian Logistic Regression Method. All dose levels of BI 754111 were co-administered with 240 mg q3w BI 754091 (the BI 754091 RPIID selected from 1381.1 phase I [Johnson, et al. ASCO-SITC 2017 abstract 212]). Enrollment in the solid tumor dose escalation portion is nearly complete. The expansion phase will use a combination dose selected from the solid tumor dose escalation. Primary endpoints in the dose escalation are the number of pts with dose-limiting toxicities and the combination MTD. The primary endpoint of the dose expansion portion is the objective response rate. Clinical trial identification: NCT03156114. Legal entity responsible for the study: Boehringer Ingelheim Pharmaceuticals, Inc. Funding: Boehringer Ingelheim Pharmaceuticals, Inc. Disclosure: M. Elgadi: Employee: Boehringer Ingelheim (Canada) Ltd./Ltee. M. Ge, C. Duffy: Employee: Boehringer Ingelheim Pharmaceuticals, Inc. R. Graeser: Employee: Boehringer Ingelheim Pharma GmbH & Co. KG. All other authors have declared no conflicts of interest.
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 | 0.001 | 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) | 0.003 | 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".