Locally Advanced Unresectable Uveal Melanoma Clinical Trial
Official title:
Neoadjuvant Tebentafusp in Patients With Locally Advanced, Unresectable Primary Uveal Melanoma
This phase II trial tests how well tebentafusp works to shrink tumors prior to primary treatment with surgery or radiation in patients with uveal (eye) melanoma that has spread to nearby tissue or lymph nodes (locally advanced) or that cannot be removed by surgery (unresectable). Tebentafusp is a drug that binds to melanoma tumor cells as well as immune cells called T-cells. This binding causes an immune response against the melanoma cells, which leads to tumor cell death. Tebentafusp has been approved for the treatment of locally advanced and unresectable uveal melanoma. Giving tebentafusp before primary treatment with surgery or radiation may help shrink the tumor, prevent the disease from spreading, or reduce the likelihood that patients will require total eye removal (called enucleation).
PRIMARY OBJECTIVE: I. To assess the efficacy of neoadjuvant tebentafusp in patients with large surgically unresectable (other than complete enucleation of eye) primary uveal melanoma. SECONDARY OBJECTIVES: I. To assess the local (eye) and systemic toxicity with tebentafusp treatment. II. To investigate the usefulness of circulating tumor-derived deoxyribonucleic acid (DNA) (ctDNA) as a biomarker for response. EXPLORATORY OBJECTIVES: I. To assess sight preservation. II. To assess the change in radiation dose to the fovea. OUTLINE: Patients receive tebentafusp intravenously (IV) over 15-20 minutes on days 1, 8, 15, and 22 of each cycle. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Within 28 days of their last dose of tebentafusp, patients undergo standard of care (SOC) primary eye treatment (plaque radiotherapy or eye enucleation), as decided by their treating physician. Patients also undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) at screening, ophthalmic ultrasound, optical coherence tomography (OCT), wide-angle fundus imaging, OCT angiography (OCTA), fluorescein angiography, orbit magnetic resonance imaging (MRI), and collection of blood samples throughout the trial, undergo biopsy and collection of aqueous humour samples at screening and on study, and undergo abdominal MRI and chest and pelvis computed tomography (CT) at screening and during follow up. After completion of primary eye treatment, patients are followed up at 3 months and then every 3 months for up to 5 years. ;