On April 22, 2021 Onconova Therapeutics, Inc. (NASDAQ: ONTX), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, reported that the first patient has been dosed in an investigator-initiated Phase 2 study to assess the efficacy and safety of rigosertib in patients with recessive dystrophic epidermolysis bullosa (RDEB)-associated locally advanced/metastatic squamous cell carcinoma (SCC) (Press release, Onconova, APR 22, 2021, View Source [SID1234578368]). The patient was dosed at the EB House Austria, a center of expertise for epidermolysis bullosa at the University Hospital Salzburg, Austria. Additional sites are anticipated to be opened in the UK and in the US to study this rare and genomically driven devastating disease.
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In this open-label investigator-initiated study, 12 patients will receive either oral or intravenous rigosertib at the clinician’s discretion given the various clinical manifestations of the disease, which may dictate the need for either oral or intravenous administration of rigosertib. These patients have skin desquamation making intravenous access difficult, or may form esophageal strictures, which make oral administration difficult. Patients will receive either oral rigosertib in four-week cycles (three weeks on, one week off) for up to 13 cycles, with 560 mg of oral rigosertib in the morning and again in the afternoon, for a total of 1,120 mg/day. Alternatively, patients will receive intravenous (IV) rigosertib as a 72-hour IV infusion on days 1, 2 and 3 of eight 2-week cycles, and on days 1, 2 and 3 of nine 4-week cycles thereafter, with each 24-hour infusion consisting of 1,800 mg of rigosertib.
The study has two primary endpoints. The first is to determine the anti-tumor activity of rigosertib in RDEB patients with advanced SCC who have failed prior standard of care through the overall response rate (ORR), defined as the proportion of patients who achieve either a complete response (CR) or a partial response (PR). The second primary endpoint is to evaluate the safety and tolerability of rigosertib in this population. Secondary study endpoints include quality of life and a biomarker analysis performed on archival tissue from all patients. Patients will be dosed for up to one year, with trial duration anticipated to be approximately two-and-a-half years.
"We are pleased with the advancement of our investigator-initiated programs with rigosertib, and to provide rigosertib in support of this important Phase 2 investigator-sponsored study," said Steven M. Fruchtman, M.D., President and Chief Executive Officer of Onconova Therapeutics. "Recessive dystrophic epidermolysis bullosa is a genetic skin blistering disease that often results in squamous cell carcinoma in severe subtypes. In this patient cohort, squamous cell carcinoma is the leading cause of death. We have previously identified polo-like kinase 1 as a therapeutic target in skin SCC, including RDEB SCC, so we are encouraged by the start of this trial. We hope rigosertib can prove beneficial to this rare patient population with a tremendous unmet medical need."
In addition to Onconova Therapeutics, the study is being supported by DEBRA International. "The aggressive course and poor prognosis of skin cancer in our patients emphasize the urgent need for potent therapies," stated Professor Johann W. Bauer, M.D., Principal investigator of the trial. "We hope that rigosertib as an innovative approach provides benefit to this devastating illness that currently lacks effective therapies."
"Basic research has provided understanding into the etiology of Recessive Dystrophic Epidermolysis Bullosa-associated cancer," stated Andrew South Ph.D., Associate Professor, Department of Dermatology & Cutaneous Biology, Thomas Jefferson University. "I would like to thank both the Debra Foundations for funding this work as well as Onconova for providing a research drug that may target the life-threatening cancers arising in these patients."