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"First in EB" Phase II trial of Rigosertib for RDEB SCC (South 3a)

Project lead Dr Andrew South
Organisation Thomas Jefferson University, Jefferson Medical College, Philadelphia, USA
Partner organizations & collaborators Prof Johann Bauer, Paracelsus Medical University Salzburg, Austria & Prof Jemima Mellerio St John’s Institute of Dermatology, St Thomas’ Hospital, London, UK
Project budget USD 398,000.00
Start date / Duration 01. Apr 2017 / -
Funder(s) / Co-Funder(s) DEBRA UK, MSAP/EBEP Recommended
Research area Skin cancer & fibrosis

Project details

Short lay summary

Squamous cell carcinoma (SCC) of the skin is the biggest cause of death in patients with Recessive Dystrophic Epidermolysis Bullosa (RDEB). Although we are beginning to understand why patients develop this fatal cancer, therapies which target RDEB SCC are urgently required.

The South group previously screened a range of small molecule inhibitors and identified a compound, Rigosertib, that exhibited significant specificity. Rigosertib induced apoptosis (cell death) in RDEB SCC cells without affecting normal RDEB skin cells in culture. Furthermore, Rigosertib inhibited the growth of RDEB SCC in vivo and showed no apparent toxicity in mouse models.

Scientific summary

The South group propose to offer a "first in EB" clinical trial of Rigosertib to assess tumour targeting and tolerability in patients with late stage, metastatic and/or unresectable SCC. In parallel they will determine whether biomarkers (cell surface markers and molecules that have been identified that cells use to communicate) predict response. If successful, this research could provide steps towards a much needed treatment option for RDEB SCC.

They aim to recruit six to ten patients with late stage SCC that have not responded to standard care. The study will take place at two European sites, Austria (Prof. Johann Bauer) and the UK (Prof. Jemima Mellerio) and will be coordinated by EB-House Austria. Patients will take oral Rigosertib continuously for a total of two weeks in a three week cycle. Conclusions regarding safety and efficacy will be drawn after six patients have completed a number of cycles of treatment or treatment has ended.

The study will also have a strong scientific element. The group will catalogue mutations (or mistakes) identified in each tumour and compare these data with patient response to treatment and results of laboratory testing. This approach will investigate patient individuality to see if any patterns can be seen. Tumour samples will be taken to investigate drug sensitivity using models and special techniques in the laboratory called immuno-histochemistry, which will look at components of the pathways that are active in SCC in RDEB patients, and which may identify or further characterise targets for treatment.

The pharmaceutical company Onconova, who manufacture Rigosertib, will be closely involved. Rigosertib is an investigational drug currently being trialled for a number of cancers and it does not yet have a licence in any therapeutic area. This study is what is termed an investigator led study, the drug will be provided by Onconova.

Strategic relevance

“New medicines are becoming available that target particular features of a given cancer, such as inhibitors that target a certain mutation. This DEBRA funded initiative will be the first clinical trial of a so-called “targeted” cancer therapy that is based on scientific data obtained from studying RDEB SCC. We are extremely excited that this new drug could be offered as a potential treatment.” Dr Andrew South

“SCC is a devastating complication for people with severe RDEB, and the treatments we can offer currently are really limited in effectiveness. This trial opens the way to newer, more targeted approaches to try and tackle these cancers and, as such, is a really exciting new direction for clinical EB research.” Dr Jemima Mellerio

Newsarticle about the first patient being treated by Rigosertib in April 2021.

More on DEBRA UK's website.



clinical Trial
Phase II
Thomas Jefferson University
St. John's Institute
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