Abstract C027: A Phase I, dose finding study of BI 754111, an anti-LAG-3 antibody, in combination with BI 754091, an anti-PD-1 antibody, in patients with advanced solid tumors: preliminary results from the microsatellite stable (MSS) metastatic colorectal cancer (mCRC) cohort
Bibliographic record
Abstract
Abstract Background: Inhibition of the PD-1 pathway is an effective immunotherapeutic approach in a subset of patients with various solid tumors and hematologic malignancies. Blockade of the PD-1 pathway leads to overexpression of other checkpoint receptors, including LAG3, potentially providing an escape pathway for tumor cells. LAG-3 signaling contributes to immune cell exhaustion, preventing T-cell proliferation. Dual blockade of PD-1 and LAG-3 has the potential to synergistically restore T-cell functionality and therefore enhance antitumor immune responses. This Phase I trial is evaluating the combination of BI 754111, an anti-LAG-3 monoclonal antibody (mAb), and BI 754091, an anti-PD-1 mAb, in patients with advanced solid tumors. Methods: This open-label, Phase I study is being conducted in two parts. Part 1 (dose-escalation) enrolled patients with advanced solid tumors; no dose limiting toxicities were reported and BI 754111 600 mg intravenous (iv) every 3 weeks (q3w) in combination with BI 754091 (240 mg iv q3w) was selected for further assessment in part 2 (dose expansion). In part 2, patients are being enrolled in 4 cohorts: 1) anti-PD-(L)1 pretreated non-small cell lung cancer (NSCLC) that progressed after having achieved benefit on previous PD-(L)1; 2) previously treated (anti-PD-[L]1 naïve) MSS mCRC; 3) anti-PD-(L)1 pretreated TMB >10 and/or MSI-h and/or dMMR solid tumors; 4) treatment-naive NSCLC with EGFR and ALK wild type tumors. Primary endpoint for the expansion cohorts is objective response. Safety and pharmacokinetics of the combination were secondary endpoints. The mCRC cohort is fully recruited; other cohorts are open to recruitment. This abstract presents data from the MSS CRC cohort. Results. 40 patients with MSS mCRC were enrolled (27 male [67.5%]; median age 56.5 years [range 25–85]; median of 3.0 prior regimens [range 1–10]) and received BI 754111 600 mg q3w in combination with BI 754091 240 mg q3w. Treatment-related AEs (TRAEs) were reported in 18 patients (45%); most commonly infusion-related reactions (10.0%), myalgia (10.0%), hypothyroidism (7.5%), diarrhea (7.5%) and arthralgia (7.5%). Grade 3/4 TRAEs occurred in 4 patients (grade 3 colitis, grade 3 maculo-papular rash, grade 4 diabetic ketoacidosis [n=2]). Treatment-emergent immune-related AEs occurred in 9 patients; of these, 4 had grade 3/4 events (colitis and maculo-papular rash [grade 3] and diabetic ketoacidosis [grade 4; n=2]). To date, 2 (5%) patients achieved a partial response, and 12 (30%) achieved stable disease. Updates will be presented. Conclusion. BI 754111 + BI 754091 was well-tolerated and showed preliminary activity in patients with previously treated MSS mCRC. Assessment of the combination in other cohorts is ongoing. Citation Format: Johanna Bendell, Susanna V Ulahannan, Quincy Chu, Manish Patel, Ben George, Renee Landsberg, Mabrouk Elgadi, Christine Duffy, Ralph Graeser, Wenbo Tang, Michael Merger, Miaomiao Ge, Melissa Johnson. A Phase I, dose finding study of BI 754111, an anti-LAG-3 antibody, in combination with BI 754091, an anti-PD-1 antibody, in patients with advanced solid tumors: preliminary results from the microsatellite stable (MSS) metastatic colorectal cancer (mCRC) cohort [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr C027. doi:10.1158/1535-7163.TARG-19-C027
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".