Rigosertib shows promise in trial for RDEB patients with advanced SCC

2 patients achieve complete treatment response in skin: Data

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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Rigosertib may hold promise for recessive dystrophic epidermolysis bullosa (RDEB) associated with advanced squamous cell carcinoma (SCC), with two patients achieving complete treatment responses in the skin, according to initial clinical trial data.

The findings were presented at the European Academy of Dermatology and Venereology (EADV) annual congress, held Oct. 11-14 in Berlin. The presentation, titled “Efficacy and Safety of Rigosertib in Patients with Recessive Dystrophic Epidermolysis Bullosa (RDEB) Associated Advanced/Metastatic Squamous Cell Carcinoma (SCC),” was given by Johann Bauer, MD, from the University Hospital Salzburg, in Austria.

Now, “eligible patients are being sought for this experimental approach,” according to the researchers.

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Dystrophic epidermolysis bullosa, or DEB for short, is caused by mutations in the COL7A1 gene, which provides instructions for the production of a part of the type VII collagen protein. Collagens confers structure to tissues and organs; type VII collagen connects the different skin layers.

In the absence of this collagen, the connections become fragile, leading to the formation of blisters and scar tissue in the skin.

People with RDEB inherit two copies of the disease-causing mutations, one from each biological parent. This EB type is characterized by skin and mucosal blistering, with patients having an increased risk of squamous cell carcinoma or SCC, a type of skin cancer.

Rigosertib, developed by Onconova Therapeutics, is being tested in clinical trials as a potential treatment for RDEB-associated SSC. The therapy is thought to work by blocking the activity of polo-like kinase 1 (PLK1), a protein involved in cell division, whose levels are increased in these patients.

In the EADV presentation, Bauer reported the results of four RDEB patients with advanced SCC resistant to treatment. All are taking part in an investigator-sponsored Phase 1/2 clinical trial (NCT03786237).

Patients received the treatment either intravenously (into-the-vein) or orally. The intravenous medication was given at a dose of 1,800 mg/day during three days, every two weeks over eight cycles, and then every week thereafter. The oral treatment was given at 560 mg twice a day, for 21 or 28 days. The route of administration considered the extent of RDEB skin and mucosal involvement, as well as patient preference.

The first patient, a 23-year-old woman with more than 29 SCC, achieved disease remission, with stable metabolic activity at week 12 of intravenous rigosertib. She later developed a bladder infection, and the medication was continue with ah dose reduction. The duration of response was 16 months.

A woman, 32, with a history of skin SCC and lymph nodes involvement was the second patient. She achieved complete skin disease remission on oral rigosertib. The patient finished the protocol of 12 months of therapy.

The third patient was a woman, 21, with several SCC tumors in the right thigh. Tissue death in a large tumor was temporarily related to IV rigosertib administration, and resulted in definitive surgical amputation.

During week 9 of treatment, a PET scan revealed metastatic progression of the disease.

Another 21-year-old woman with SCC on her right knee and lymph node involvement received oral rigosertib. However, due to low levels of rigosertib in the blood, she was switched to intraveneous treatment and remained on the study until such time as it was presented.

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“RDEB-associated SCC is a devastating disease with few if any treatment options for advanced patients,” said Steven Fruchtman, MD, Onconova’s president and CEO, said in a company press release.

“We are very pleased for additional data on the potential use of rigosertib in patients with RDEB-associated SCC to be presented as a ‘late breaker’ at EADV 2023,” Fruchtman said.

Bauer said researchers were “keen to further enroll other potential patients on this study.”

“I am pleased to share the initial encouraging patient experience with rigosertib at this conference,” Bauer said, adding that the preliminary data “indicate [rigosertib] as a potential treatment for [skin SCC] in RDEB patients.”

The treatment also is being tested in a Phase 1 clinical trial (NCT04177498) in the U.S. That trial also is assessing both oral and intravenous forms of the therapy in people with RDEB and SSC.

The study began in 2021 at Thomas Jefferson University, in Philadelphia.

“We believe that rigosertib’s profile and impact on key cell signaling pathway targets, including PLK-1 kinase, could make rigosertib a very attractive approach for this indication and other cancers,” Fruchtman said.