Rigosertib for RDEB SCC

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Current Projects, EB Cancer Therapy, Whole Body Treatment
About This Project

Rigosertib for recessive dystrophic epidermolysis bullosa-associated squamous cell carcinoma

Lay summary

Squamous cell carcinoma (SCC) of the skin is the biggest cause of death in patients with recessive dystrophic epidermolysis bullosa (RDEB). Although emerging data are identifying why patients suffer this fatal complication, therapies which target RDEB SCC are urgently required.

In previous lab-based research, rigosertib was shown to eliminate RDEB SCC cells without affecting normal skin cell. Based on this data, a “first in EB” clinical trial commenced to assess tolerability and tumor targeting in RDEB patients with late stage, metastatic and / or unresectable (incapable of being surgically removed) SCC. The first patient to be treated with rigosertib in Europe has shown a complete response, with all three target lesions being eliminated after six months.

Cure EB funding expands this clinical work to fund the treatment of one patient in the US and up to three patients in the UK. If successful, the data from this research would form the basis of a license application for the use of rigosertib as a first line treatment in RDEB SCC.

*The initiation of the clinical trial in the US was funded by DEBRA America.

Scientific Summary

Identification of PLK1 as a target in RDEB SCC and the drug rigosertib for treatment of RDEB SCC have previously been published.

The first RDEB SCC patient to receive rigosertib did so via intravenous infusion on April 21st 2021. After 3 months of treatment two of the three target lesions were undetectable by CT/MRI scans while the third lesion was stable. After 6 months all lesions had responded, and the patient also reported other lesions which previously exhibited changes in pain profiles with the onset of cancer had also responded. Side effects were limited to cystitis, which was relieved with medication, and cancer site pain during infusions. The patient remains on treatment and continued use of rigosertib will be reviewed at the end of the trail period, after 12 months.

The aim of this project is to treat one RDEB SCC patient with intravenous rigosertib in the US. The trial is up and running with all regulatory and staffing components in place, and one patient has begun treatment with oral rigosertib. However, pharmacokinetic analysis shows significantly lower plasma concentrations following oral administration compared with intravenous administration. In addition, RDEB patients often have gastrointestinal complications, so it is unknown how well a patient with RDEB will absorb rigosertib, or whether many patients could swallow the large capsules.

Publications

Efficacy and Safety of Rigosertib in Patients with Recessive Dystrophic Epidermolysis Bullosa Associated Advanced/Metastatic Cutaneous Squamous Cell Carcinoma. British Journal of Dermatology 2025

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