613 Oral rigosertib demonstrates preliminary efficacy in the treatment of recessive dystrophic epidermolysis bullosa-associated cutaneous squamous cell carcinoma

Recessive dystrophic epidermolysis bullosa (RDEB) is a severe genodermatosis caused by mutations in collagen 7 (COL7A1) leading to generalized skin and mucosal blistering. RDEB patients develop cutaneous squamous cell carcinomas (cSCCs) which are often aggressive, metastatic, and a common cause of death. There are limited effective treatment options for RDEB-associated advanced cSCCs. Our group previously identified the Ser/Thr polo-like kinase-1 (PLK-1) as a therapeutic target for RDEB cSCC and matched the allosteric PI3K/PLK-1 inhibitor ON-01910 (rigosertib) as the most specific agent for targeting RDEB cSCCs in the laboratory. These preclinical data were the backbone for the phase II open-label clinical trial of either oral or intravenous (IV) rigosertib in patients with RDEB-associated cSCCs refractory to standard of care in the US and Austria. The first patient enrolled in the IV arm in Austria demonstrated complete histological and clinical remission. Here we present interim findings from the oral arm at Thomas Jefferson University. A 32-year-old female with RDEB and multiple cSCCs and metastatic disease involving the lymph nodes whose prior treatments included surgical excision, systemic targeted therapy (cetuximab) and immunotherapy (pembrolizumab) was enrolled. At baseline, she had active disease in her left elbow measuring 1589 mm2. After 4 cycles of oral rigosertib, the tumor exhibited complete clinical resolution. Side effects included hematuria and urinary frequency, recognized side effects of rigosertib. In conclusion, both the oral and IV formulations of rigosertib have shown preliminary efficacy in the treatment of RDEB-associated cSCCs. Additional patients are being sought to enter the trial (NCT04177498).