Abstract LB118: Evidence of tumor response in orbital lesions treated with tebentafusp in metastatic uveal melanoma patients
Bibliographic record
Abstract
Abstract Background: Tebentafusp, a bispecific (gp100 x CD3) ImmTAC that can redirect T cells to target gp100+ melanoma cells, has shown a superior overall survival (OS) benefit compared to investigator choice for HLA-A*02:01+ patients (pts) with untreated metastatic uveal melanoma (mUM). Although local control rates for primary UM are high, a minority of patients with mUM have recurrent or untreated orbital disease. Here we present safety and efficacy from tebentafusp treated mUM pts with orbital lesions including intraocular lesions. Methods: Tumor response according to RECIST v1.1 and ocular Adverse Events (AEs) were assessed in a pooled analysis of mUM pts with orbital lesions from 3 tebentafusp trials: IMCgp100-01 (Phase (Ph) 1/2, 19 2L+ mUM pts), IMCgp100-102 (Ph 1/2 2L+ mUM, 146 pts) and IMCgp100-202 (Ph3 1L mUM, 245 tebentafusp pts). Pre-treatment biopsies, taken prior to the IMCgp100-202 trial, were analyzed by immunohistochemistry for gp100 and CD3+ or CD8+ T cell infiltration prior to tebentafusp treatment. Results: In the 3 clinical trials, 12 mUM pts with radiologically detectable orbital lesions received tebentafusp, the majority of which were intra-ocular. All lesions were stable or had achieved shrinkage. 5/12 pts had orbital target lesions (TL), of which 4/5 had achieved tumor shrinkage (best % change -3 to -40) and 1/5 had no change in tumor size. All non-target orbital lesions were stable or achieved a complete response. 9 eye disorder AEs occurred in 5 pts, the majority of which were G1. The most common (7/9) AEs were extra-ocular local edema. One G3 eye pain AE, in a post eviscerated eye, did not resolve and occurred in the setting of disease progression resulting in treatment discontinuation. All other eye disorder AEs recovered and none led to tebentafusp discontinuation. 37 primary UM and 195 liver metastasis baseline biopsies were evaluated. Expression of gp100 in primary UM and mUM was high (95% and 80%, respectively). CD3+ and CD8+ T cell numbers were generally lower in primary UM compared to liver metastasis (median CD3: 231 and 504 cells/mm2, p=0.035; CD8: 121 and 238 cells/mm2, p=0.53, respectively). Conclusions: Following tebentafusp treatment, tumor reduction or stabilization of all orbital lesions including intra-ocular lesions were observed. Most AEs were extra-ocular mild local edema. Primary UM showed a high level of gp100 expression and also T cell infiltration. These preliminary signals of tebentafusp activity in orbital disease, including intra-ocular lesions, suggest a role for tebentafusp as a neoadjuvant therapy in UM and warrant further investigation. Citation Format: Marcus O. Butler, Takami Sato, Friedegund Meier, Ramakrishna Edukulla, Sarah Stanhope, Fraser S. Peck, Jessica C. Hassel. Evidence of tumor response in orbital lesions treated with tebentafusp in metastatic uveal melanoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB118.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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".