Neoadjuvant Tebentafusp for Uveal Melanoma

Regression of primary uveal melanoma after Tebentafusp treatment in 20% of treated patients.

Regression is defined as ≥ 20% reduction in tumor volume. All estimates of rates will be presented with corresponding 95% exact confidence intervals. For regression rate, the method of Atkinson and Brown will be used to allow for the two-stage design.

Incidence of adverse events (AEs)

Will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events (AE) version 5.0. All estimates of rates will be presented with corresponding 95% exact confidence intervals. AEs will be reported for each dose level and presented as tables of frequency of AEs by body system and by worse severity grade observed. AE term start and end date, severity, seriousness, outcome, action taken regarding study drugs and relationship to each study drug will also be reported. The summary tables will also discuss AEs leading to death and AEs leading to study drug(s) discontinuation. Tables should indicate related and unrelated events. Laboratory data will be presented by dose level at each observation time. Values outside normal limits will be identified and summarized by frequency distribution.

Detection of plasma circulating tumor-derived deoxyribonucleic acid (ctDNA) and correlation of antitumor response

Plasma of patients will be collected for all patients at baseline (within 28 days of first dose), cycle 2 day 1, post-tebentafusp (within 14 days of last dose), and at the 3 month post-treatment evaluation. ctDNA response will be measured (defined as ≥0.3 log reduction) in ctDNA-evaluable patients as measured using Signatera assay and correlated with eye tumor regression.

Detection of aqueous humor ctDNA and correlation of antitumor response

Aqueous humor of patients will be collected at baseline and post-tebentafusp; if no ctDNA is detectable in the aqueous humor after 5 patients we will stop collecting aqueous ctDNA for the rest of the patients. ctDNA response will be measured (defined as ≥0.3 log reduction) in ctDNA-evaluable patients as measured using Signatera assay and correlated with eye tumor regression.

Assessment of visual acuity loss at baseline (prior to Tebentafusp treatment), prior to plaque brachytherapy, and 3) following plaque brachytherapy (after resolution of any radiation side effects/edema).

Ophthalmological examination for assessment of disease: this will be performed within 48 hours prior to Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 2 Day 1. Additional ophthalmological examinations may be performed if clinically indicated. All ophthalmological examinations must be performed and interpreted by a qualified ocular oncologist. Examination will include clinical eye examination, ophthalmic ultrasound, wide-angle fundus imaging, and optical coherence tomography

Change in radiation dose to the fovea.

Change in modeled radiation dose at critical eye structures before and after neoadjuvant Tebentafusp therapy

Enucleation vs plaque brachytherapy post-treatment

Assessment of proportion of patients who had planned enucleation prior to therapy, but following Tebentafusp treatment were suitable for plaque brachytherapy.