Uveal Melanoma

Neoadjuvant RBP-01 in patients with primary uveal melanoma.

This is an open label study evaluating lifileucel (LN-144) in patients with metastatic uveal melanoma.

The goal of this clinical trial is to investigate the safety and feasibility of neoadjuvant immunotherapy for patients with high-risk uveal melanoma. The main question is: \- Is neoadjuvant treatment with nivolumab and ipilimumab safe and feasible for patientt with high-riks uveal melanoma? In addition pathological response, distant metastases-free survival, overall survival and immunological changes in the tumor microenviroenment after therapy will be assesed.

At least 50% of patients with high-risk primary uveal melanoma will develop a recurrence following treatment of the primary tumour. Observation is currently the standard of care in the non-metastatic setting. Tebentafusp is the first agent proven to improve overall survival in patients with metastatic uveal melanoma in a randomized trial. Based on the results in the advanced setting, it is hypothesized that treatment with tebentafusp may reduce the risk of development of disease recurrence.

The purpose of this study is to see if giving participants quisinostat will prevent participants' uveal melanoma tumor from spreading. The researchers want to find out the effects that quisinostat has on participants' condition.

This is a Phase 3, randomized, multi-center, open-label study of neoadjuvant darovasertib in subjects with primary non-metastatic uveal melanoma (OptimUM-10)

Only 20% of familial uveal melanomas are explained by a hereditary predisposition, implying the presence of as yet unknown hereditary predispositions. This hypothesis is reinforced by epidemiological studies revealing an excess risk of prostate cancer, thyroid cancer and leukemia in patients who have developed uveal melanoma, even though these cancers are not part of the tumor spectrum of known hereditary predispositions to uveal melanoma (BAP1, MBD4). The identification of new candidate genes, once validated, would enable us to offer these families appropriate surveillance.

This phase I trial studies the side effects and best dose of modified immune cells (IL13Ralpha2 CAR T cells) after a chemotherapy conditioning regimen for the treatment of patients with stage IIIC or IV melanoma or solid tumors that have spread to other places in the body (metastatic). The study agent is called IL13Ralpha2 CAR T cells. T cells are a special type of white blood cell (immune cells) that have the ability to kill tumor cells. The T cells are obtained from the patient's own blood, grown in a laboratory, and modified by adding the IL13Ralpha2 CAR gene. The IL13Ralpha2 CAR gene is inserted into T cells with a virus called a lentivirus. The lentivirus allows cells to make the IL13Ralpha2 CAR protein. This CAR has been designed to bind to a protein on the surface of tumor cells called IL13Ralpha2. This study is being done to determine the dose at which the gene-modified immune cells are safe, how long the cells stay in the body, and if the cells are able to attack the cancer.

This study seeks to better understand the liver's immune response to receiving chemotherapy agent melphalan through Percutaneous Hepatic Perfusion (PHP) for patients with Uveal Melanoma that has metastasized to the liver.

This research will have a significant impact on the overall management of those cancer patients and their family members who are at risk for hereditary cancer due to germline inactivation of BAP1. Our study will ultimately facilitate the development of novel screening, prevention and treatment strategies for these individuals with the syndrome. Because the vast majority of UM develop in pre-existing nevi, characterization of individuals at high risk for development of UM will allow closer screening and earlier intervention which would improve the treatment outcome not only for retaining vision but also for overall survival. Similarly in patients with germline BAP1 mutation CM develops in premalignant atypical melanocytic lesions and careful follow up of these patients will improve the outcome of their disease. In addition this study could have impact on the management of patients with personal and/or family history of several other cancers reported in patients with germline BAP1 mutation such as mesothelioma, renal cell carcinoma, cholangiocarcinoma, hepatocellular carcinoma, meningioma and basal cell carcinoma.

This is a phase II open-label, single-arm, multi-center study of tebentafusp in HLA- A\*0201 positive previously untreated (1L) untreated metastatic uveal melanoma (mUM) with an integrated circulating tumor DNA (ctDNA) biomarker.

To assess subject-centric real-world evidence of QoL outcomes in subjects enrolled in the global Phase 3 AU-011-301 clinical trial.

This open-label clinical trial will evaluate the safety and tolerability of NN3201 in subjects with advanced and/or metastatic solid tumors known to express c-Kit.

Biomarkers search for early diagnosis of liver metastases in patients with uveal melanoma who benefit from a follow-up tailored to their personalized risk of relapse.

A recent clinical trial found that after 36 months, patients taking tebentafusp had a median survival of 21.6 months, compared to 16.9 months for those in the control group. Since recruitment for tebentafusp in metastatic uveal melanoma (mUM) has ended, a new trial is starting to test whether adding IL-2 can help overcome resistance to tebentafusp and improve its effectiveness. This study aims to answer: 1. Can combining tebentafusp with IL-2 improve tumor response and overall survival? 2. What are the benefits and side effects of this combination therapy? All participants will receive both IL-2 and tebentafusp in a 28-day treatment cycle. The dosing schedule is as follows: Cycle1: Day1-3 IL-2 Day4 Tebentafusp Day 10 IL-2 Day 11 Tebentafusp Day 17 IL-2 Day 18 Tebentafusp Day 24 IL-2 Day 25 Tebentafusp Cycle 2 \& thereafter Day 1 IL-2 Day 2 Tebentafusp Day 8 IL-2 Day 9 Tebentafusp Day 15 IL-2 Day 16 Tebentafusp Day 22 IL-2 Day 23 Tebentafusp

Uveal melanoma (UM) is the most common type of cancer inside the eyes of adults. Almost half of all patients diagnosed with UM will eventually develop metastases. Once metastases occur, the median patient survival is short. In this trial, we will test if treatment with Melatonin after primary tumor diagnosis can prevent or delay the development of metastases. 100 patients diagnosed with primary UM will be randomized to either treatment with Melatonin tablets (20 mg at night), or to a control group. Both groups will be followed for 5 years. At 5 years, the number of patients that have developed metastases in the Melatonin and control groups will be compared (primary outcome measure).

Uveal melanoma is the most common primary intraocular malignancy in adults. Despite successful control of the primary tumor, metastatic disease will develop in approximately 35%-50% of the patients within 10 years. The liver is the most common site for metastases, and about 50% of the patients will have isolated liver metastases. These metastases are generally refractory to systemic chemotherapy and the median survival for patients with liver metastases is about 6 months. Regardless of treatment, the mortality rate is approximately 90% at 2 years with only about 1% of the patients surviving more than 5 years. The primary objective with this study is to evaluate progression-free survival in patients with uveal melanoma liver metastases randomized to either percutaneous hepatic perfusion (PHP) in combination with ipilimumab and nivolumab or ipilimumab and nivolumab only. Secondary objectives include further efficacy and safety analysis, as well as biomarker discovery.

Evaluate the safety and tolerability of treatment with autologous tumor infiltrating lymphocytes (TIL) administered via hepatic arterial infusion and preconditioning with percutaneous hepatic perfusion in patients with liver metastases (but not restricted to) of malignant melanoma

Background: Uveal melanoma (UM) is a common primary ocular malignancy associated with limited overall survival in the advanced stage of the disease. Fundamental breakthrough regarding the management of the disease and the overall-survival have not yet been achieved. Studies with large cohorts are difficult to perform due to limited patient numbers, therefore retrospective analyses are of great potential to gain further knowledge in a disease with high clinical needs. Aim: The proposed project is a register for patients with UM treated at the Department of Ophthalmology and Optometry at the Medical University of Vienna between 01.01.1997 and 31.12.2021. Patients and Methods: Patients treated for UM at the Department of Ophthalmology and Optometry at the Medical University of Vienna between 01.01.1997 and 31.12.2021 will be included in the register. Information on the baseline characteristics, survival times and course of the disease will be gathered via retrospective chart review and saved in a password-secured database.

This Expanded Access Program aims to: 1. Provide access to tebentafusp for mUM patients. 2. Provide access to tebentafusp for patients, who were on the control arm of the randomized controlled Phase II trial (IMCgp100-202) and were unable to crossover during the specified window. 3. Ensure that patients, who are benefiting from tebentafusp treatment while participating in an ongoing Immunocore sponsored clinical study (e.g., IMCgp100-102 or IMCgp100-201), may continue tebentafusp treatment on this Programme once the ongoing trial has met all of its key primary and secondary objectives.

Uveal melanoma is the most common primary intraocular tumor in adults. The local treatment is effective, but patients still die of metastatic disease. It has been shown that early diagnosis of a few isolated metastases can result in a clean surgical excision of the metastases and an extension of the expected survival from 7-12 months to over 10 years on some patients. Many serum biomarkers are employed in Oncology. It makes sense to try the relevant ones in the diagnosis of metastatic uveal melanoma. The investigators hypothesis is that a soluble serum biomarker level changes upon development of metastatic disease either by secretion by the tumor cells themselves or by their environment. Detection of changes in biomarker level may lead to the diagnosis of metastases before they can be detected by imaging modalities, thus allowing for early treatment of the metastases and a better chance of success.