Increasing optimism for sufferers of aggressive cancer type
Uveal melanoma is a rare cancer arising within the uveal tract of the eye. Unfortunately, approximately 50% of patients develop metastases which are resistant to current therapies. In such cases the overall survival can be as short as one year. iOnctura’s Chief Medical Officer, Michael Lahn discusses how iOnctura is developing a new therapy for this aggressive form of cancer.
Q.
What is uveal melanoma, its symptoms, and the challenges in treating it?
As is often the case with many terms in medicine, the word “uveal” is derived from the Latin word “uva” (“grape”). It refers to the reddish-blue and grape-like appearance of this layer when isolated from the eye. The uvea is the vascular middle layer of the eye and is traditionally divided into three areas, from front to back: iris, ciliary body and choroid.
Uveal melanoma is a type of cancer that develops from melanocytes in the uvea. It occurs more frequently in fair-skinned individuals with grey or blue eyes. Some people may have no symptoms and the cancer can be detected during routine eye tests. Others may experience issues such as flashing lights, blurred vision, or a shadow in one eye. Treatment options are limited and often disfiguring, such as the removal of the affected eye (enucleation), which then leads to significant psychological and practical impacts due to impaired vision. Furthermore, in half of cases the disease metastasizes outside the eye, most commonly to the liver.
The PI3K signalling pathway is one of the most commonly dysregulated pathways in cancer. In fact, it’s often referred to as a “Master Switch” of cancer.
Q.
What are the recent breakthroughs in treating uveal melanoma?
Before 2022 there were no approved therapies for uveal melanoma and many patients received immunotherapies, such as pembrolizumab or nivolumab. In January 2022, the FDA approved Immunocore’s Kimmtrak (tebentafusp-tebn) for HLA-A*02:01-positive unresectable and metastatic uveal melanoma. In August 2023 this was followed by the approval of Delcath Systems’ Hepzato (melphalan for injection/hepatic delivery system) for eligible adults with unresectable liver metastases from uveal melanoma.
Kimmtrak requires that patients are positive in HLA-A*02:01, which may be present in 30-50% of Caucasians. For those not eligible or who do not respond to Kimmtrak, options are limited. Where possible immunotherapies or clinical trials are an option. Also, in specialized centers, Hepzato’s Delcath can be offered.
Q.
What is iOnctura’s therapeutic approach to uveal melanoma?
iOnctura’s roginolisib is a new type of phosphatidylinositol 3-kinase δ (PI3Kδ) inhibitor which acts as an allosteric modulator. Allosteric modulation changes the 3D structure of a protein thereby affecting its activity in a unique way. The PI3K signalling pathway is one of the most commonly dysregulated pathways in cancer. In fact, it’s often referred to as a “Master Switch” of cancer. Roginolisib has a multi-modal effect on cancer: directly preventing cancer cell proliferation, enhancing an anti-tumour immune response via blocking regulatory T-cells and enhancing cytotoxic T cells.
Clinical data show that roginolisib treatment is well tolerated, leads to an increase in cytotoxic T cells, and results in promising overall survival in uveal melanoma.
Q.
What future plans does iOnctura have for roginolisib?
iOnctura plans to further investigate roginolisib in a randomized Phase II study which will begin later this year. In addition, we plan to evaluate roginolisib in other indications such as non-small-cell lung cancer and primary myelofibrosis.
