Characterization of liver function tests (LFTs) following tebentafusp (tebe) in previously treated (2L+) metastatic uveal melanoma (mUM) patients (pts).
Bibliographic record
Abstract
e21513 Background: Tebe is a bispecific gp100-targeted T cell receptor fusion protein that can redirect polyclonal T cells to target gp100+ cells leading to T cell activation and release of inflammatory mediators. Hepatocytes do not express gp100 and tebe did not redirect T cells against normal hepatocytes in preclinical in vitro studies. However, since most mUM pts have liver metastases, tebe may result in secondary effects from localized tumor-related inflammation. Here we describe LFT kinetics and outcomes for pts in the IMCgp100-102 study (NCT02570308). Methods: 127 HLA-A*02:01+ pts with 2L+ mUM received tebe, administered weekly at the RP2D following intra-patient dose escalation (C1D1: 20μg; C1D8: 30μg; C1D15+: 68μg). Pts were eligible if ALT/AST ≤ 3 x ULN and bilirubin ≤ 1.5 x ULN. LFTs were measured at baseline (BL) and weekly prior to each dose using local laboratories. AE grading was based on CTCAE v4.03. This analysis was conducted on the primary analysis snapshot dated 04Jun20. Results: At BL,125/127 (98%) pts had ALT/AST ≤ grade(G)1 and 122/127 (96%) had liver metastasis. 68/127 (54%) had an increase in post-BL grade for ALT, AST or both. Of these 48/68 (71%) increased to G1, 9/68 (13%) to G2, 7/68 (10%) to G3, and 4/68 (6%) to G4. 67 of these 68 pts (99%) had liver metastasis and most had largest liver metastasis > 3cm (38 pts > 3 cm, 29 pts < 3cm and 1 pt without). ALT/AST increases occurred early in treatment in 36/68 (53%) including at Dose 1 (12/68; 18%), Dose 2 (10/68; 15%), or Dose 3 (14/68; 21%). In the other 32/68 pts (47%), ALT/AST increases occurred at or after Dose 4 (4-65), and most of these events (21/32; 66%) were associated temporally with increase in size of liver metastases. Among the 11 pts with G3/4 ALT/AST increases post-BL, most pts experienced these events early (Doses 1-3) (8/11; 73%) and in the context of either increase in size of liver metastases / disease progression or biliary obstruction (9/11; 82%). Most pts, 60/68 (88%), continued treatment despite an increase in ALT/AST grade. Among 8 pts who discontinued treatment, 3 were due to disease progression and 3 were due to adverse events. Median time for ALT/AST to return to BL was 9 days and there were no temporal increases in albumin or INR. Conclusions: Approximately 1/2 of tebe treated pts experienced an increase in post-BL CTCAE grade for ALT/AST. Among these pts, most ALT/AST increases were mild. Most of the pts with G3/4 ALT/AST increase (9/11) were explained by increase in size of liver metastases or biliary obstruction. Increase in LFT are not unusual at time of disease progression in mUM given high frequency of liver metastases. In summary, ALT/AST increases occurred early in about half of the pts, were generally self-limiting, permitted treatment to continue, and did not appear to impact liver synthetic function (INR/Albumin). Clinical trial information: NCT02570308.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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) | 0.001 | 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 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".