The study showed positive anti-cancer results, supporting the development of an oral formulation of the investigational therapy.
Kevetrin is a small-molecule activator of p53, a key protein across human cancer. The p53 gene is a tumor suppressor — a type of gene that stops tumor growth. Mutations in the p53 gene, which prevent the p53 protein from exerting its anti-cancer effects, have been linked to human tumors more than any other gene in the genome.
By binding to p53, Kevetrin can lead to the death of cancer cells.
The study (NCT03042702) evaluated Kevetrin’s ability to modulate p53 in late stage, platinum-resistant/refractory ovarian cancer patients. Modulation of p53 was demonstrated in the analysis of the first ovarian cancer patients treated with the lowest dose.
Patients receiving higher levels of the therapy also received more frequent dosing — three times a week — which was followed by standard-of-care treatment after the trial’s conclusion.
The data also showed that Kevetrin alters the level of genes that control cell cycle modulation, which is implicated in cancer cell growth. An analysis of tumor biopsies showed that a total of nine intravenous Kevetrin infusions over three weeks also changed the level of the activated form of p53 protein.
The results confirmed findings in cell studies and in a completed Phase 1 study in advanced solid tumors (NCT01664000).
“This study delivered multiple insights into how Kevetrin modulates the p53 protein and affects related molecular pathways,” Arthur P. Bertolino, MD and PhD, the chief medical office and president of Innovation, said in a press release.
Overall, anti-cancer treatment with Kevetrin demonstrated positive efficacy and a positive pharmacological profile. The company believes these features make the therapy an ideal candidate for oral delivery, which is more convenient to patients and may allow more frequent dosing. Innovation is now focusing on developing an oral formulation and finding a development partner for the treatment candidate.
“If we successfully transition to oral dosing of Kevetrin, we believe the therapeutic effect will be maximized, providing important benefits to cancer patients in need — beyond the ultimate convenience of oral delivery. An effective orally-delivered p53-modulating drug has the potential to transform cancer care,” Bertolino said.
The therapy candidate was granted orphan drug status by the U.S. Food and Drug Administration (FDA) for the treatment of ovarian cancer, pancreatic cancer, and retinoblastoma. This designation covers potential treatments for disorders affecting fewer than 200,000 patients in the U.S., or for diseases that are not expected to recover the costs of product development and marketing.
The FDA also granted Kevetrin rare pediatric disease designation for childhood retinoblastoma.