Carvajal, Richard D, Butler, Marcus O, Shoushtari, Alexander N, Hassel, Jessica C, Ikeguchi, Alexandra, Hernandez-Aya, Leonel, Nathan, Paul, Hamid, Omid, Piulats, Josep M, Rioth, Matthew et al (show 11 more authors)
(2022)
Clinical and molecular response to tebentafusp in previously treated patients with metastatic uveal melanoma: a phase 2 trial.
Nature Medicine, 28 (11).
2364-+.
Abstract
<jats:title>Abstract</jats:title><jats:p>In patients with previously treated metastatic uveal melanoma, the historical 1 year overall survival rate is 37% with a median overall survival of 7.8 months. We conducted a multicenter, single-arm, open-label phase 2 study of tebentafusp, a soluble T cell receptor bispecific (gp100×CD3), in 127 patients with treatment-refractory metastatic uveal melanoma (NCT02570308). The primary endpoint was the estimation of objective response rate based on RECIST (Response Evaluation Criteria in Solid Tumours) v1.1. Secondary objectives included safety, overall survival, progression-free survival and disease control rate. All patients had at least one treatment-related adverse event, with rash (87%), pyrexia (80%) and pruritus (67%) being the most common. Toxicity was mostly mild to moderate in severity but was greatly reduced in incidence and intensity after the initial three doses. Despite a low overall response rate of 5% (95% CI: 2–10%), the 1 year overall survival rate was 62% (95% CI: 53–70%) with a median overall survival of 16.8 months (95% CI: 12.9–21.3), suggesting benefit beyond traditional radiographic-based response criteria. In an exploratory analysis, early on-treatment reduction in circulating tumour DNA was strongly associated with overall survival, even in patients with radiographic progression. Our findings indicate that tebentafusp has promising clinical activity with an acceptable safety profile in patients with previously treated metastatic uveal melanoma, and data suggesting ctDNA as an early indicator of clinical benefit from tebentafusp need confirmation in a randomized trial.</jats:p>
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Humans, Melanoma, Uveal Neoplasms, Progression-Free Survival |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 21 Oct 2022 08:28 |
| Last Modified: | 07 Mar 2023 16:20 |
| DOI: | 10.1038/s41591-022-02015-7 |
| Open Access URL: | https://www.nature.com/articles/s41591-022-02015-7 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3165690 |
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