Digest of new data from Uveal Melanoma research presented at ASCO'20

UM Cure 2020 followed the ASCO'20 Annual Meeting and brings you a digest of 19 studies with uveal melanoma (UM) patients, 11 only with uveal melanoma patients and 8 studies including mostly other melanoma subtypes or other cancers.

Exclusive Uveal Melanoma studies: two negative trials, two potential future treatment for liver metastases, one new technique to improve tumour-infiltrating lymphocytes (TIL) preparation, two new trials recruiting patients in UC, and four studies published as abstract only, all described below

There were two negative clinical trials (i.e. experimental drugs that failed to prove effect against in uveal melanoma) presented at poster sessions, both with oral tyrosine kinase inhibitors (i.e. drugs that stop intracellular processes of tumour growth): ulixertinib that failed to show effect in UM metastatic patients (NCT03417739) and crizotinib that failed to reduce the disease recurrence in patients with high-risk UM after treatment of the eye (NCT02223819).

Dr. David Minor, from California Pacific Medical Center Research Institute, presented preliminary data from 15 UM patients with liver metastases treated with liver internal radiation (using yttrium90 radiation, via hepatic artery infusion) followed by ipilimumab and nivolumab. This therapy appears feasible if radiation to normal liver is limited to 35Gy and ipilimumab dose is 1mg/kg, and objective tumour responses were seen. This study is still recruiting in USA (NCT02913417).

Researchers of The University of Texas MD Anderson Cancer Center presented four posters. Dr. Sapna Patel, presented encouraging initial results from the 15 UM patients with liver metastases treated in a phase 1 basket trial (i.e. a clinical trial that tests how well a new drug or other substance works in patients who have different types of cancer) to determine a safe dose of PV-10 - a small molecule autolytic immunotherapy - reporting regression or stabilization in 83% of the injected liver lesions. The trial is still ongoing and recruiting in USA (NCT00986661). Other researcher from the team presented a new method for growth of TIL in culture, harvested from primary tumour or metastatic lesions for experimental administration. Ultimately, they presented the protocols of two active clinical trials in the USA: i) hepatic arterial infusion of SLC45A2-specific cytotoxic T cells (immune cells proved to be effective against UM cell lines in laboratory) for UM liver metastases (NCT03068624); ii) a phase II study of adjuvant ipilimumab in combination with nivolumab in patients with high-risk ocular melanoma (NCT03528408).

Four additional studies were presented as abstract only. One study showed that limited (≤5) liver metastasis or lung metastasis (without liver metastasis) at diagnosis predict favourable clinical outcomes in metastatic UM (38 vs 15 months of survival) and that the occurrence of such metastasis following a significantly longer time from primary diagnosis suggests a subtype of indolent behaviour. Researchers from Thomas Jefferson University presented preliminary data from adjuvant sunitinib and valproic acid as safe and tolerable treatment for high-risk uveal melanoma, but treatment impact on reduction in relapse rate is unknown since the trial is still recruiting (NCT02068586). Dr. John Park, from Macquarie University, presented data from the evaluation for blood circulating tumour DNA - ctDNA - in metastatic UM patients receiving experimental early phase clinical trial of LXS196 (NCT02601378); this research suggests that baseline ctDNA correlates with baseline LDH level and disease volume and ctDNA at the end of treatment predicted clinical benefit to this drug. Ultimately, researchers from UCLA presented a study of molecular profiling of 45 young UM patients, concluding that the prognosis of these patients was much better than predicted by this molecular testing, and much better than expected regardless of gene expression profile or cytogenetic testing.

Studies including mostly other melanoma subtypes and other cancers: 

Two real-world data studies (i.e. research studies from patients treated outside clinical trials in normal clinical practice) reinforced that immune checkpoint inhibitors (ICI) do not work as they do in cutaneous melanoma (1 and 2). On the other side, researchers from Boston University School of Medicine, report in a meta-analysis, that UM patients are those with the lowest discontinuation rate due to toxicity of ICI combination - ipilimumab and nivolumab (11% vs 46% in cutaneous), what goes in line with some reports defending that the degree of toxicity is somehow related with the anti-tumour effect in immunotherapy. Dr. Mark Middleton, from University of Oxford, presented preliminary data from a clinical trial testing RP1 - an oncolytic herpes virus - combined with nivolumab in melanoma, including 4 patients with ocular melanoma (NCT03767348). Researchers from UCLA Stein Eye Institute reported a high incidence of ocular immune related adverse events in melanoma patients treated with ICI (including UM patients in whom visual impairment might be already a big issue).

Researchers presented preliminary data from two phase 1 trials with two experimental immunotherapies. These trials involved very few patients with ocular melanoma, are still recruiting, and will continue to next phases (NCT03543813 - USA only, and NCT03782467 - Denmark and Sweden).

Ultimately, researchers from University of Florida, presented the methodology of the ongoing phase II trial testing niraparib - an oral PARP inhibitor - in BAP1 mutated tumours, as uveal melanoma (NCT03207347).

Despite being a rare disease without effective therapeutic alternatives in the metastatic setting, many researchers around the globe are working on finding new approaches for the treatment of UM patients. 

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