Concurrent Local Therapy Extends Clinical Benefit of Tebentafusp in Metastatic Uveal Melanoma Patients

Authors

Tristan L. Lim
Kamaneh Montazeri
Eric Wehrenberg-Klee
Antoine Desilets
Rino S. Seedor, Thomas Jefferson UniversityFollow
Marlana Orloff, Thomas Jefferson UniversityFollow
Takami Sato, Thomas Jefferson UniversityFollow
Michael Caplan
Mariam El-Ashmawy
Benjamin Izar
Shaheer Khan
Inderjit Mehmi
Aleigha Lawless
Theodore S. Hong
Omid Hamid
Richard D. Carvajal
Alexander Shoushtari
Ryan J. Sullivan

Document Type

Article

Publication Date

10-1-2025

Comments

This article is the author’s final published version in Oncologist, Volume 30, Issue 10, 2025, Article number oyaf323.

The published version is available at https://doi.org/10.1093/oncolo/oyaf323. Copyright © The Author(s) 2025.

Abstract

BACKGROUND: Tebentafusp has significantly improved overall survival in HLA-A*02:01+ metastatic uveal melanoma (mUM) patients even in those with a best objective response of progressive disease. Thus, strategies to maintain tebentafusp therapy are critical. Here, we examine the efficacy and safety of adding concurrent local therapy (CLT) to tebentafusp upon radiological progression with tebentafusp alone.

PATIENTS AND METHODS: This multicenter retrospective study included mUM patients treated with tebentafusp and CLT, consisting of extrahepatic soft tissue irradiation and liver-directed therapies (LDTs). Efficacy of target and nontarget sites were assessed per RECIST version 1.1. PFS with tebentafusp alone (PFS1) was compared to that after adding CLTs to tebentafusp upon progression (PFS1+PFS2). ctDNA responses were explored.

RESULTS: Of the 30 eligible patients, 21 (70%) received concurrent LDT, 7 (23%) had extrahepatic irradiation, and 2 (7%) had both. The objective response rate (ORR) was 12% (95% CI, 3-32) for tebentafusp alone and 28% (95% CI, 14-47) after adding CLTs. The disease-control rate with tebentafusp alone was 44% (95% CI, 25-65) vs 63% (95% CI, 44-78) after CLT. Median PFS1 was 5.8 months (95% CI, 2.8-13.4), while median PFS1+PFS2 was 14.8 months (95% CI, 9.2-NA). CLT thereby allowed treatment beyond progression with tebentafusp for approximately 9 months. Two patients (66%) had decreased ctDNA with tebentafusp alone, while 4 (100%) had decreased ctDNA after CLT. There were no treatment discontinuations due to toxicities from tebentafusp with CLT.

CONCLUSIONS: CLT with tebentafusp was well-tolerated, extending the duration of tebentafusp benefit in a highly selected mUM population. This merits further studies to assess clinical utility.

Recommended Citation

Lim, Tristan L.; Montazeri, Kamaneh; Wehrenberg-Klee, Eric; Desilets, Antoine; Seedor, Rino S.; Orloff, Marlana; Sato, Takami; Caplan, Michael; El-Ashmawy, Mariam; Izar, Benjamin; Khan, Shaheer; Mehmi, Inderjit; Lawless, Aleigha; Hong, Theodore S.; Hamid, Omid; Carvajal, Richard D.; Shoushtari, Alexander; and Sullivan, Ryan J., "Concurrent Local Therapy Extends Clinical Benefit of Tebentafusp in Metastatic Uveal Melanoma Patients" (2025). Kimmel Cancer Center Faculty Papers. Paper 165.
https://jdc.jefferson.edu/kimmelccfp/165

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

41021466

Language

English